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Wranke, Anika ; Heidrich, Benjamin ; Ernst, Stefanie ; Serrano, Beatriz Calle ; Caruntu, Florin Alexandru ; Curescu, Manuela Gabriela ; Yalcin, Kendal ; Gürel, Selim ; Zeuzem, Stefan ; Erhardt, Andreas ; Lüth, Stefan ; Papatheodoridis, George V. ; Bremer, Birgit ; Stift, Judith ; Grabowski, Jan ; Kirschner, Janina ; Port, Kerstin ; Cornberg, Markus ; Falk, Christine S. ; Dienes, Hans-Peter ; Hardtke, Svenja ; Manns, Michael P. ; Yurdaydin, Cihan ; Wedemeyer, Heiner
Background: Hepatitis delta frequently leads to liver cirrhosis and hepatic decompensation. As treatment options are limited, there is a need for biomarkers to determine disease activity and to predict the risk of disease progression. We hypothesized that anti-HDV IgM could represent such a marker.
Methods: Samples of 120 HDV-infected patients recruited in an international multicenter treatment trial (HIDIT-2) were studied. Anti-HDV IgM testing was performed using ETI-DELTA-IGMK-2-assay (DiaSorin). In addition, fifty cytokines, chemokines and angiogenetic factors were measured using multiplex technology (Bio-Plex System). A second independent cohort of 78 patients was studied for the development of liver-related clinical endpoints (decompensation, HCC, liver transplantation or death; median follow up of 3.0 years, range 0.6–12).
Results: Anti-HDV IgM serum levels were negative in 18 (15%), low (OD<0.5) in 76 (63%), and high in 26 (22%) patients of the HIDIT-2 cohort. Anti-HDV IgM were significantly associated with histological inflammatory (p<0.01) and biochemical disease activity (ALT, AST p<0.01). HDV replication was independent from anti-HDV IgM, however, low HBV-DNA levels were observed in groups with higher anti-HDV IgM levels (p<0.01). While high IP-10 (CXCL10) levels were seen in greater groups of anti-HDV IgM levels, various other antiviral cytokines were negatively associated with anti-HDV IgM. Associations between anti-HDV IgM and ALT, AST, HBV-DNA were confirmed in the independent cohort. Clinical endpoints occurred in 26 anti-HDV IgM positive patients (39%) but in only one anti-HDV IgM negative individual (9%; p = 0.05).
Conclusions: Serum anti-HDV IgM is a robust, easy-to-apply and relatively cheap marker to determine disease activity in hepatitis delta which has prognostic implications. High anti-HDV IgM levels may indicate an activated interferon system but exhausted antiviral immunity.
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Kong, Xiang-Zhen ; Mathias, Samuel R. ; Guadalupe, Tulio ; Abé, Christoph ; Agartz, Ingrid ; Akudjedu, Theophilus N. ; Andre, Aleman ; Saud, Alhusaini ; Allen, Nicholas B. ; Ames, David ; Andreassen, Ole A. ; Arias Vásquez, Alejandro ; Armstrong, Nicola J. ; Bergo, Felipe ; Bastin, Mark E. ; Batalla, Albert ; Bauer, Jochen ; Baune, Bernhard T. ; Baur, Ramona ; Biederman, Joseph ; Blaine, Sara K. ; Boedhoe, Premika ; Bøen, Erlend ; Bose, Anushree ; Bralten, Janita ; Brandeis, Daniel ; Brem, Silvia ; Brodaty, Henry ; Bröhl, Henrieke ; Brooks, Samantha J. ; Buitelaar, Jan K. ; Bürger, Christian ; Bülow, Robin ; Calhoun, Vince D. ; Calvo, Anna ; Canales-Rodrı́guez, Erick Jorge ; Canive, Jose M. ; Cannon, Dara M. ; Caparelli, Elisabeth C. ; Castellanos, Francisco X. ; Cavalleri, Gianpiero L. ; Cendes, Fernando ; Chaim-Avancini, Tiffany Moukbel ; Chantiluke, Kaylita ; Chen, Qun-lin ; Chen, Xiayu ; Cheng, Yuqi ; Christakou, Anastasia ; Clark, Vincent P. ; Coghill, David ; Connolly, Colm G. ; Conzelmann, Annette ; Cόrdova-Palomera, Aldo ; Cousijn, Janna ; Crow, Tim ; Cubillo, Ana ; Dannlowski, Udo ; de Bruttopilo, Sara Ambrosino ; Zeeuw, Patrick de ; Deary, Ian J. ; Delanty, Norman ; Demeter, Damion V. ; Di Martino, Adriana ; Dickie, Erin W ; Dietsche, Bruno ; Doan, N. Trung ; Doherty, Colin P. ; Doyle, Alysa ; Durston, Sarah ; Earl, Eric ; Ehrlich, Stefan ; Ekman, Carl Johan ; Elvsåshagen, Torbjørn ; Epstein, Jeffery N. ; Fair, Damien A. ; Faraone, Stephen V. ; Fatouros-Bergman, Helena ; Fernndez, Guillen ; Busatto Filho, Geraldo ; Flyckt, Lena ; Forster, Katharina ; Jean-Paul, Fouche ; Foxe, John J. ; Fuentes-Claramonte, Paola ; Fullerton, Janice M. ; Garavan, Hugh ; Garcia, Danielle do Santos ; Gotlib, Ian H. ; Goudriaan, Anna E. ; Grabe, Hans Jörgen ; Groenewold, Nynke A. ; Grotegerd, Dominik ; Gruber, Oliver ; Gurholt, Tiril ; Haavik, Jan ; Hahn, Tim ; Hansell, Narelle K. ; Harris, Mathew A. ; Hartman, Catharina ; Hernandez, Maria del Carmen Valdes ; Heslenfeld, Dirk ; Hester, Robert ; Hibar, Derrek Paul ; Ho, Beng-Choon ; Ho, Tiffany C. ; Hoekstra, Pieter J. ; van Holst, Ruth J. ; Hoogman, Martine ; Hovik, Marie F. ; Howells, Fleur M. ; Hugdahl, Kenneth ; Huyser, Chaim ; Ingvar, Martind ; Irwin, Lourdes ; Ishikawa, Akari ; James, Anthony ; Jahanshad, Neda ; Jernigan, Terry L. ; Jönsson, Erik G. ; Kahler, Claas ; Kaleda, Vasily ; Kelly, Clare ; Kerich, Michael ; Keshavan, Matcheri S ; Khadka, Sabin ; Kircher, Tilo ; Kohls, Gregor ; Konrad, Kerstin ; Korucuoglu, Ozlem ; Krämer, Bernd ; Krug, Axel ; Kwon, Jun Soo ; Lambregts-Rommelse, Nanda ; Landén, Mikael ; Lázaro, Luisa ; Lebedeva, Irina ; Lenroot, Rhoshel ; Lesch, Klaus-Peter J. ; Li, Qinqin ; Lim, Kelvin O. ; Liu, Jia ; Lochner, Christine ; London, Edythe D. ; Lonning, Vera ; Lorenzetti, Valentina ; Luciano, Michelle ; Luijten, Maartje ; Lundervold, Astri J. ; Mackey, Scott ; MacMaster, Frank P. ; Maingault, Sophie ; Malpas, Charles B. ; Malt, Ulrik F. ; Mataix-Cols, David ; Martin-Santos, Rocio ; Mayer, Andrew R. ; McCarthy, Hazel ; Mitchell, Philip B. ; Mueller, Bryon A. ; Maniega, Susana Munoz ; Mazoyer, Bernard ; McDonald, Colm ; McLellan, Quinn ; McMahon, Katie L. ; McPhilemy, Genevieve ; Momenan, Reza ; Morales, Angelica M. ; Narayanaswamy, Janardhanan C. ; Moreira, José Carlos Vasques ; Nerland, Stener ; Nestor, Liam ; Nigg, Joel T. ; Nordvik, Jan-Egil ; Novotny, Stephanie ; Oberwelland, Eileen ; O’Gorman, Ruth L. ; Oosterlaan, Jaap ; Oranje, Bob ; Orr, Catherine ; Overs, Bronwyn ; Pauli, Paul ; Paulus, Martin ; Plessen, Kerstin ; Polier, Georg von ; Pomarol-Clotet, Edith ; Qiu, Jiang ; Radua, Joaquim ; Ramos-Quiroga, J. Antoni ; Reddy, Y.C. Janardhan ; Reif, Andreas ; Roberts, Gloria ; Rosa, Pedro ; Rubia, Katya ; Sacchet, Matthew D. ; Sachdev, Perminder S. ; Salvador, Raymond ; Schmaal, Lianne ; Schweren, Lisanne ; Seidman, Larry J. ; Seitz, Jochen ; Serpa, Mauricio Henriques ; Shaw, Philip ; Shumskaya, Elena ; Silk, Timothy J. ; Simmons, Alan N. ; Simulionyte, Egle ; Sinha, Rajita ; Sjoerds, Zsuzsika ; Smelror, Runar Elle ; Soliva, Joan Carlos ; Solowij, Nadia ; Sponheim, Scott R. ; Stein, Dan J. ; Stein, Elliot A. ; Stevens, Michael ; Strike, Lachlan T. ; Sudre, Gustavo ; Sui, Jing ; Tamm, Leanne ; Temmingh, Hendrik S. ; Thoma, Robert J. ; Tomyshev, Alexander S. ; Tronchin, Giulia ; Turner, Jessica A. ; Uhlmann, Anne ; van Erp, Theo G.M. ; van den Heuvel, Odile ; Meer, Dennis van der ; Eijk, Liza van ; Vance, Alasdair ; Veer, Ilya M. ; Veltman, Dick J. ; Venkatasubramanian, Ganesan ; Vilarroya, Oscar ; Vives-Gilabert, Yolanda ; Voineskos, Aristotle N. ; Völzke, Henry ; Vuletic, Daniella ; Walitza, Susanne ; Walter, Henrik ; Walton, Esther ; Wardlaw, Joanna M. ; Wen, Wei ; Westlye, Lars T. ; Whelan, Christopher D. ; White, Tonya ; Wiers, Reinout W. ; Wright, Margaret J. ; Wittfeld, Katharina ; Yang, Tony T. ; Yasuda, Clarissa L. ; Yoncheva, Yuliya ; Yucel, Murat ; Yun, Je-Yeon ; Zanetti, Marcus Vinicius ; Zhen, Zonglei ; Zhu, Xing-xing ; Ziegler, Georg Christoph ; Zierhut, Kathrin ; De Zubicaray, Greig ; Zwiers, Marcel P. ; Glahn, David C. ; Franke, Barbara ; Crivello, Fabrice ; Tzourio-Mazoyer, Nathalie ; Fisher, Simon E. ; Thompson, Paul M. ; Francks, Clyde ; Farde, Lars ; Engberg, Goran ; Erhardt, Sophie ; Cervenka, Simon ; Schwieler, Lilly ; Piehl, Fredrik ; Collste, Karin ; Victorsson, Pauliina ; Malmqvist, Anna ; Hedberg, Mikael ; Orhan, Funda