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1. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, Nancy L., Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M., Bis, Joshua C., Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C., Lemstra, Afina W., Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A. L., Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anaïs, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L., Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M., Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G., Kunkle, Brian W., Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B., Chillotti, Caterina, Reynolds, Chandra A., Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L., Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K., Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L., Vogelgsang, Jonathan, Pineda, Juan A., Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A., Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M. Arfan, Deniz-Naranjo, M. Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A., Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M., Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J., Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H., Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T., Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M., Seidu, Nazib M., Banaj, Nerisa, Armstrong, Nicola J., Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Mecocci, Patrizia, Hoffmann, Per, Holmans, Peter A., Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N., Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A. L., Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J., Álvarez, Victoria, Lleó, Alberto, Real, Luis M., Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D., Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M., Mather, Karen A., Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A., Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M., Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J., and Ruiz, Agustín

Published
2023
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2. New insights into the genetic etiology of Alzheimer’s disease and related dementias

Author

Bellenguez, Céline, Küçükali, Fahri, Jansen, Iris E, Kleineidam, Luca, Moreno-Grau, Sonia, Amin, Najaf, Naj, Adam C, Campos-Martin, Rafael, Grenier-Boley, Benjamin, Andrade, Victor, Holmans, Peter A, Boland, Anne, Damotte, Vincent, van der Lee, Sven J, Costa, Marcos R, Kuulasmaa, Teemu, Yang, Qiong, de Rojas, Itziar, Bis, Joshua C, Yaqub, Amber, Prokic, Ivana, Chapuis, Julien, Ahmad, Shahzad, Giedraitis, Vilmantas, Aarsland, Dag, Garcia-Gonzalez, Pablo, Abdelnour, Carla, Alarcón-Martín, Emilio, Alcolea, Daniel, Alegret, Montserrat, Alvarez, Ignacio, Álvarez, Victoria, Armstrong, Nicola J, Tsolaki, Anthoula, Antúnez, Carmen, Appollonio, Ildebrando, Arcaro, Marina, Archetti, Silvana, Pastor, Alfonso Arias, Arosio, Beatrice, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa, Baquero, Miquel, Barral, Sandra, Beiser, Alexa, Pastor, Ana Belén, Below, Jennifer E, Benchek, Penelope, Benussi, Luisa, Berr, Claudine, Besse, Céline, Bessi, Valentina, Binetti, Giuliano, Bizarro, Alessandra, Blesa, Rafael, Boada, Mercè, Boerwinkle, Eric, Borroni, Barbara, Boschi, Silvia, Bossù, Paola, Bråthen, Geir, Bressler, Jan, Bresner, Catherine, Brodaty, Henry, Brookes, Keeley J, Brusco, Luis Ignacio, Buiza-Rueda, Dolores, Bûrger, Katharina, Burholt, Vanessa, Bush, William S, Calero, Miguel, Cantwell, Laura B, Chene, Geneviève, Chung, Jaeyoon, Cuccaro, Michael L, Carracedo, Ángel, Cecchetti, Roberta, Cervera-Carles, Laura, Charbonnier, Camille, Chen, Hung-Hsin, Chillotti, Caterina, Ciccone, Simona, Claassen, Jurgen AHR, Clark, Christopher, Conti, Elisa, Corma-Gómez, Anaïs, Costantini, Emanuele, Custodero, Carlo, Daian, Delphine, Dalmasso, Maria Carolina, Daniele, Antonio, Dardiotis, Efthimios, Dartigues, Jean-François, de Deyn, Peter Paul, de Paiva Lopes, Katia, de Witte, Lot D, Debette, Stéphanie, Deckert, Jürgen, and del Ser, Teodoro

Subjects
Biochemistry and Cell Biology, Genetics, Biological Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurodegenerative, Alzheimer's Disease, Human Genome, Prevention, Aging, Brain Disorders, Acquired Cognitive Impairment, Neurosciences, Genetic Testing, 2.1 Biological and endogenous factors, Aetiology, Neurological, Alzheimer Disease, Cognitive Dysfunction, Genome-Wide Association Study, Humans, tau Proteins, EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

Published
2022

5. A metagenome-wide association study of HIV disease progression in HIV controllers

Author

Real, Luis Miguel, Sáez, María E., Corma-Gómez, Anais, Gonzalez-Pérez, Antonio, Thorball, Christian, Ruiz, Rocío, Jimenez-Leon, María Reyes, Gonzalez-Serna, Alejandro, Gasca-Capote, Carmen, Bravo, María José, Royo, José Luis, Perez-Gomez, Alberto, Camacho-Sojo, María Inés, Gallego, Isabel, Vitalle, Joana, Bachiller, Sara, Gutierrez-Valencia, Alicia, Vidal, Francisco, Fellay, Jacques, Lichterfeld, Mathias, and Ruiz-Mateos, Ezequiel

Published
2023
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8. Long or complicated mpox in patients with uncontrolled HIV infection

Author

Corma‐Gómez, Anaïs, primary, Cabello, Alfonso, additional, Orviz, Eva, additional, Morante‐Ruiz, Miguel, additional, Ayerdi, Oskar, additional, Al‐Hayani, Aws, additional, Muñoz‐Gómez, Ana, additional, Santos, Ignacio De Los, additional, Gómez‐Ayerbe, Cristina, additional, Rodrigo, David, additional, Riestra, Sandra De la Rosa, additional, Reus‐Bañuls, Sergio, additional, Silva‐Klug, Ana, additional, Galindo, María José, additional, Santos, Marta, additional, Serrano‐Fuentes, Miriam, additional, Faro‐Míguez, Naya, additional, Pérez‐Camacho, Inés, additional, Corona‐Mata, Diana, additional, Morano, Luis, additional, López‐Ruz, Miguel Ángel, additional, Montero, Marta, additional, Anaya‐Baz, Blanca, additional, Merino, Dolores, additional, Castillo‐Navarro, Antonia, additional, Pineda, Juan A., additional, and Macías, Juan, additional

Published
2024
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9. The absence of seroconversion after exposition to hepatitis C virus is not related to KIR-HLA genotype combinations (GEHEP-012 study)

Author

Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, Junta de Andalucía, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), European Commission, Servicio Andaluz de Salud, Royo, José Luis [0000-0003-2024-4363], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis Miguel [0000-0003-4932-7429], Martín-Sierra, Carmen, Bravo, María José, Sáez, María Eugenia, Rojas, Itziar de, Santos, Marta, Martín-Carmona, Jesica, Corma-Gómez, Anaïs, González-Serna, Alejandro, Royo, José Luis, Pineda, Juan A., Rivero, Antonio, Rivero-Juárez, Antonio, Macías, Juan, Real, Luis Miguel, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, Junta de Andalucía, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), European Commission, Servicio Andaluz de Salud, Royo, José Luis [0000-0003-2024-4363], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis Miguel [0000-0003-4932-7429], Martín-Sierra, Carmen, Bravo, María José, Sáez, María Eugenia, Rojas, Itziar de, Santos, Marta, Martín-Carmona, Jesica, Corma-Gómez, Anaïs, González-Serna, Alejandro, Royo, José Luis, Pineda, Juan A., Rivero, Antonio, Rivero-Juárez, Antonio, Macías, Juan, and Real, Luis Miguel

Abstract

[Background & aims] It has been reported that specific killer-cell immunoglobulin-like receptors (KIRs) and HLA genotype combinations, such as KIR2DS4/HLA-C1 with presence of KIRDL2 or KIRDL3, homozygous KIRDL3/HLA-C1 and KIR3DL1/≥2HLA-Bw4, are strongly associated with the lack of active infection and seroconversion after exposition to hepatitis C virus (HCV)., [Objective] To determine whether these KIR-HLA combinations are relevant factors involved in that phenotype., [Patients and methods] In this retrospective case-control study, genotype data from a genome-wide association study previously performed on low susceptibility to HCV-infection carried out on 27 high-risk HCV-seronegative (HRSN) individuals and 743 chronically infected (CI) subjects were used. HLA alleles were imputed using R package HIBAG v1.2223 and KIR genotypes were imputed using the online resource KIR*IMP v1.2.0., [Results] It was possible to successfully impute at least one KIR-HLA genotype combination previously associated with the lack of infection and seroconversion after exposition to HCV in a total of 23 (85.2%) HRSN individuals and in 650 (87.5%) CI subjects. No KIR-HLA genotype combination analyzed was related to the HRSN condition., [Conclusions] Our results suggest that those KIR-HLA genotype combinations are not relevant factors involved in the lack of infection and seroconversion after exposition to HCV. More studies will be needed to completely understand this phenotype.

Published
2024

10. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, Nancy L., Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M., Bis, Joshua C., Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C., Lemstra, Afina W., Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A. L., Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anaïs, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L., Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M., Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G., Kunkle, Brian W., Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B., Chillotti, Caterina, Reynolds, Chandra A., Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L., Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K., Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L., Vogelgsang, Jonathan, Pineda, Juan A., Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A., Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M. Arfan, Deniz-Naranjo, M. Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A., Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M., Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J., Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H., Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T., Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M., Seidu, Nazib M., Banaj, Nerisa, Armstrong, Nicola J., Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Mecocci, Patrizia, Hoffmann, Per, Holmans, Peter A., Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N., Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A. L., Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J., Álvarez, Victoria, Lleó, Alberto, Real, Luis M., Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D., Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M., Mather, Karen A., Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A., Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M., Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J., and Ruiz, Agustín

Published
2021
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12. Kinetics of emergence of liver complications in hepatitis C virus infected patients and advanced fibrosis, with and without HIV-coinfection, after sustained virological response

Author

Corma-Gómez, Anaïs, Macías, Juan, Téllez, Francisco, Morano, Luis, Rivero, Antonio, Serrano, Miriam, Ríos, María José, Vera-Méndez, Francisco Jesús, Santos, Marta, Real, Luis Miguel, Palacios, Rosario, Santos, Ignacio de Los, Geijo, Paloma, Imaz, Arkaitz, Merino, Dolores, Galindo, Maria José, Reus-Bañuls, Sergio, López-Ruz, Miguel Ángel, Galera, Carlos, and Pineda, Juan A.

Published
2021
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13. Reduced neutralizing antibody response to SARS‐CoV‐2 vaccine booster dose in people living with HIV with severe immunosuppression

Author

Corma‐Gómez, Anaïs, primary, Fernández‐Fuertes, Marta, additional, Viñuela, Laura, additional, Domínguez, Carmen, additional, Santos, Martos, additional, Fuentes‐López, Ana, additional, Rojas, Almudena, additional, Fernández‐Pérez, Nieves, additional, Martín‐Carmona, Jessica, additional, Serrano‐Conde, Esther, additional, Real, Luis M., additional, Mendoza, Joaquín, additional, Macías, Juan, additional, Pineda, Juan A., additional, and García, Federico, additional

Published
2023
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14. A metagenome-wide association study of HIV disease progression in HIV controllers

Author

Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Universidad de Sevilla. Departamento de Fisiología, Junta de Andalucía, European Union (UE), European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Agencia Estatal de Investigación. España, Real, Luis Miguel, Sáez, María E., Corma Gómez, Anaïs, González Pérez, Antonio, Thorball, Christian, Ruiz Laza, Rocío, Jiménez León, María Reyes, González-Serna Martín, Manuel Alejandro, Bachiller, Sara, Ruiz Mateos, Ezequiel, Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Universidad de Sevilla. Departamento de Fisiología, Junta de Andalucía, European Union (UE), European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Agencia Estatal de Investigación. España, Real, Luis Miguel, Sáez, María E., Corma Gómez, Anaïs, González Pérez, Antonio, Thorball, Christian, Ruiz Laza, Rocío, Jiménez León, María Reyes, González-Serna Martín, Manuel Alejandro, Bachiller, Sara, and Ruiz Mateos, Ezequiel

Abstract

Some HIV controllers experience immunologic progression with CD4+ T cell decline. We aimed to identify genetic factors associated with CD4+ T cell lost in HIV controllers. A total of 561 HIV controllers were included, 442 and 119 from the International HIV controllers Study Cohort and the Swiss HIV Cohort Study, respectively. No SNP or gene was associated with the long-term non-progressor HIV spontaneous control phenotype in the individual GWAS or in the meta-analysis. However, SNPs previously associated with natural HIV control linked to HLA-B (rs2395029 [p = 0.005; OR = 1.70], rs59440261 [p = 0.003; OR = 1.78]), MICA (rs112243036 [p = 0.011; OR = 1.45]), and PSORS1C1 loci (rs3815087 [p = 0.017; OR = 1.39]) showed nominal association with this phenotype. Genetic factors associated with the long-term HIV controllers without risk of immunologic progression are those previously related to the overall HIV controller phenotype.

Published
2023

15. Burden of significant liver damage in people living with HIV after microelimination of the hepatitis C virus

Author

Red Española de Investigación en SIDA, European Commission, Instituto de Salud Carlos III, Junta de Andalucía, Santos, Marta, Corma-Gómez, Anaïs, Fernández-Fuertes, Marta, González-Serna, A., Rincón, Pilar, Real, Luis Miguel, Pineda, Juan A., Macías Sánchez, Juan, Red Española de Investigación en SIDA, European Commission, Instituto de Salud Carlos III, Junta de Andalucía, Santos, Marta, Corma-Gómez, Anaïs, Fernández-Fuertes, Marta, González-Serna, A., Rincón, Pilar, Real, Luis Miguel, Pineda, Juan A., and Macías Sánchez, Juan

Abstract

[Background] Once HIV/HCV-coinfection microelimination has been virtually achieved in some countries, there is no information about the burden of liver disease among people living with HIV (PLWH). The aim of this study was to define the current prevalence and causes of significant liver damage (SLD) in PLWH., [Methods] Cross-sectional study including 619 PLWH. SLD was defined as liver stiffness (LS) ≥ 7.2 kPa measured by transient elastography. Nonviral liver damage (NVLD) was considered if there was no evidence injury due to chronic hepatitis C virus (HCV) infection, active hepatitis B (HBV) or E virus infections., [Results] One hundred and twelve of 619 (18.2%) PLWH showed SLD, including 34/112 (5.5%) with LS ≥14 kPa. 72/112 (64.3%) had cured HCV infection, 4/112 (3.6%) active HBV infection, and 2/112 HBV/prior HCV coinfection. Thus, 40 (35.7%) showed NVLD. Metabolic associated steatohepatitis (MASH) was present in 29/40 (72.5%) of patients with NVLD, alcoholic liver damage in 2/40 (2.5%) and mixed steatohepatitis in 5/40 (12.5%)., [Conclusions] After HIV/HCV microelimination the burden of liver damage is high among PLWH. Persistent injury after HCV is a very frequent cause of SLD. However, NVLD, mainly due to MASH, is also a common condition in this population.

Published
2023

17. Reduced neutralizing antibody response to SARS-CoV-2 vaccine booster dose in people living with HIV with severe immunosuppression

Author

Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Corma-Gómez, Anaïs, Fernández-Fuertes, Marta, Viñuela, Laura, Domínguez, Carmen, Santos, Marta, Fuentes-López, Ana, Rojas, Almudena, Fernández-Pérez, Nieves, Martín-Carmona, Jesica, Serrano-Conde, Esther, Real, Luis Miguel, Mendoza, Joaquín, Macías, Juan, Pineda, Juan A., García, Federico, Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Corma-Gómez, Anaïs, Fernández-Fuertes, Marta, Viñuela, Laura, Domínguez, Carmen, Santos, Marta, Fuentes-López, Ana, Rojas, Almudena, Fernández-Pérez, Nieves, Martín-Carmona, Jesica, Serrano-Conde, Esther, Real, Luis Miguel, Mendoza, Joaquín, Macías, Juan, Pineda, Juan A., and García, Federico

Abstract

The aim of this study was to assess the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) vaccines among people living with HIV (PLWH) with severe immunosuppression, after a booster dose. The design was a case–control study nested in a prospective cohort of PLWH. All patients with CD4 cell count <200 cells/mm3 who had received additional dose of messenger RNA (mRNA) COVID-19 vaccine, after a standard immunization scheme were included. Control group: patients age- and sex-matched, with CD4 ≥ 200 cells/mm3, in the ratio of 2:1. Antibody response to a booster dose (anti-S levels 33.8 ≥ BAU/mL) and neutralizing activity against SARS-CoV-2 B.1, B.1.617.2, and Omicron BA.1, BA.2, and BA.5 strains were assessed after the booster shot. Fifty-four PLWH were included, 18 with CD4 counts < 200 cells/mm3. Fifty-one (94%) showed response to a booster dose. Response was less frequent in PLWH with CD4 < 200 cells/mm3 than in those with CD4 counts ≥ 200 cells/mm3 (15 [83%] vs. 36 [100%], p = 0.033). In the multivariate analysis, CD4 counts ≥ 200 cells/mm3 [incidence rate ratio (IRR) = 18.1 (95% confidence interval [CI]: 16.8–19.5), p < 0.001] was associated with a higher probability of showing antibody response. Neutralization activity against SARS-CoV-2 B.1, B.1.617, BA.1, and BA.2 strains was significantly inferior among individuals with CD4 counts < 200 cells/mm3. In conclusion, among PLWH with CD4 counts < 200 cells/mm3, the immune response elicited by mRNA additional vaccine dose is reduced.

Published
2023

18. Response to glecaprevir/pibrentasvir in HIV/HCV-coinfected patients in clinical practice

Author

Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Servicio Andaluz de Salud, Centros de Investigación Biomédica en Red (España), Ministerio de Ciencia e Innovación (España), Fundación para la Investigación en Salud, Gonzalez-Serna, Alejandro, Corma-Gómez, Anaïs, Téllez, Francisco, Corona-Mata, Diana, Ríos-Villegas, María José, Merino, Dolores, Galera, Carlos, Collado-Romacho, Antonio Ramón, Santos, Ignacio de los, Cucurull, Josep, Santos, Marta, García-Martín, Sofía, Rivero, Antonio, Real, Luis Miguel, Macías, Juan, Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Servicio Andaluz de Salud, Centros de Investigación Biomédica en Red (España), Ministerio de Ciencia e Innovación (España), Fundación para la Investigación en Salud, Gonzalez-Serna, Alejandro, Corma-Gómez, Anaïs, Téllez, Francisco, Corona-Mata, Diana, Ríos-Villegas, María José, Merino, Dolores, Galera, Carlos, Collado-Romacho, Antonio Ramón, Santos, Ignacio de los, Cucurull, Josep, Santos, Marta, García-Martín, Sofía, Rivero, Antonio, Real, Luis Miguel, and Macías, Juan

Abstract

[Objectives] HIV infection has been associated with lower rates of sustained viral response (SVR) with direct-acting antivirals (DAAs). There are few data on glecaprevir/pibrentasvir (G/P) in HIV/HCV coinfection outside clinical trials., [Methods] The HEPAVIR-DAA cohort, which recruits HIV/HCV-coinfected patients (NCT02057003) and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are two concurrent ongoing multicentre cohorts of patients receiving anti-HCV treatment. Patients starting G/P included in those cohorts were analysed. Overall SVR (ITT), discontinuations due to adverse effects, and dropouts were evaluated and compared between both cohorts., [Results] Of the 644 patients who started G/P with evaluable SVR, 132 were HIV/HCV coinfected. Overall SVR rates were 487/512 (95.1%) in HCV-monoinfected patients versus 126/132 (95.5%) in HIV/HCV-coinfected patients (P = 1.000). One patient (0.8%) relapsed, and another (0.8%) discontinued treatment due to side effects. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected versus HCV-monoinfected patients. The main reason for not reaching SVR among HIV/HCV-coinfected patients was premature dropout linked to active drug use., [Conclusions] G/P in HIV/HCV coinfection was highly effective and tolerable in clinical practice. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected compared with HCV-monoinfected patients but active drug use is still a barrier to reach HCV microelimination.

Published
2023

19. Poor increase on HAV vaccination coverage among people living with HIV after an immunization-based intervention

Author

Real, Luis Miguel [0000-0003-4932-7429], Macías Sánchez, Juan [0000-0002-4778-790X], Pineda, Juan A. [0000-0002-3751-0296], Corma-Gómez, Anaïs, Real, Luis Miguel, Fernández-Fuertes, Marta, González-Serna, Alejandro, Oliver, Noemi, Ortega, Jesús, Rincón, Pilar, Rodríguez-Pineda, Elena, Santos, Marta, Trigo-Rodríguez, Marta, Macías Sánchez, Juan, Pineda, Juan A., Real, Luis Miguel [0000-0003-4932-7429], Macías Sánchez, Juan [0000-0002-4778-790X], Pineda, Juan A. [0000-0002-3751-0296], Corma-Gómez, Anaïs, Real, Luis Miguel, Fernández-Fuertes, Marta, González-Serna, Alejandro, Oliver, Noemi, Ortega, Jesús, Rincón, Pilar, Rodríguez-Pineda, Elena, Santos, Marta, Trigo-Rodríguez, Marta, Macías Sánchez, Juan, and Pineda, Juan A.

Abstract

[EN] Objectives: To assess HAV serologic and vaccination status among people who live with HIV (PLWH), and to evaluate the impact of a vaccination-based strategy on HAV-negative patients in Seville, Spain. Methods: Study with two time-overlapping phases: (i) cross-sectional study of HAV immunity prevalence among PLWH followed at a Spanish hospital between August 2019 and March 2020. (ii) Patients seronegative for HAV, reliably unvaccinated were included in a before-and-after quasi-experimental study, with an intervention focused on HAV vaccination according to national recommendations in force. Results: Six hundred and fifty-six patients were included, of which 111 [17%, 95% confidence interval (95% CI) 14–20%] were seronegative for HAV. Of these, 48 [43% (95% CI, 34–53%)] individuals were MSM. The absence of HAV immunity was attributed in 69 [62% (95% CI, 52–71%)] patients to non-referral to vaccination, followed by lack of achievement of a correct vaccination scheme [n = 26; 23% (95% CI, 16–32%)]. After the program implementation, 96 [15% (95% CI, 12–18%)] individuals were seronegative (17% vs. 15%, p = 0.256), of whom 42 [41% (95% CI, 32–51%)] were MSM. The absence of immunity after the intervention was mainly attributed to: adherence failure in 23 [24.0% (95% CI, 15.8–33.7%)] patients, on-course immunization scheme in 34 [33% (95% CI, 24–43%)] individuals and pending appointment at the vaccine delivery unit in 20 [20.8% (95% CI, 13.2–30.3%)] patients. Conclusions: A sizeable proportion of PLWH remains susceptible for HAV infection in future outbreaks. A program based on referral to the vaccine delivery unit yields poor results, largely due to program adherence failures. New strategies are needed to increase HAV vaccination coverage., [ES] Objetivos: Evaluar la prevalencia de inmunidad frente al VHA en personas que viven con VIH así como el impacto de una intervención basada en la vacunación de pacientes seronegativos frente al VHA. Métodos: Estudio con dos fases solapadas en el tiempo: 1) transversal de prevalencia de inmunidad frente al VHA en personas que viven con VIH seguidas en un hospital de tercer nivel, entre agosto de 2019 y el inicio de las medidas nacionales de contención de la epidemia por SARS-CoV-2, marzo de 2020. 2) Cuasiexperimental, con una intervención centrada en la vacunación frente a VHA de pacientes seronegativos, en la unidad responsable de esta. Resultados: Ciento once (17%, [95% IC, 14-20%]) de los 656 pacientes incluidos eran seronegativos frente al VHA. Las principales causas de la ausencia de inmunidad fueron: 69 (62% [95% IC, 52-71%]) individuos no derivados a la unidad responsable de la vacunación; 26 pacientes (23% [95% CI, 16-32%]) no completaron el esquema vacunal. Tras la intervención, 96 (15% [95% IC, 12-18%]) pacientes continuaron siendo seronegativos frente al VHA (comparada con la prevalencia basal, p = 0,256), 42 (18% [95% IC, 13-23%]) eran HSH. Las principales causas de la ausencia de inmunidad fueron: 26 (23% [95% IC, 15-32%]) individuos presentaron fallos de adherencia al circuito vacunal; 34 (33% [95% IC, 24-43%]) pacientes habían recibido una sola dosis; 22 (22% [95% IC, 14-31%]) seguían sin una primera valoración por parte de la unidad responsable de la vacunación. Conclusiones: Una proporción considerable de personas que viven con VIH, particularmente HSH, sigue siendo susceptible a la infección por VHA. La derivación sistemática a la unidad responsable de la vacunación se traduce en modestos incrementos de la prevalencia de inmunidad. Son necesarias nuevas estrategias para aumentar la cobertura vacunal.

Published
2023

20. Hepatic steatosis after switching to integrase inhibitor-based regimens does not parallel short-term weight gain

Author

González-Serna, Alejandro, Macías, Juan, Rincón, Pilar, Arriaza, María José, Corma-Gómez, Anaïs, Santos, Marta, Fernández-Fuertes, Marta, Pineda, Juan A., Real, Luis Miguel, González-Serna, Alejandro, Macías, Juan, Rincón, Pilar, Arriaza, María José, Corma-Gómez, Anaïs, Santos, Marta, Fernández-Fuertes, Marta, Pineda, Juan A., and Real, Luis Miguel

Abstract

We studied hepatic steatosis in people with HIV (PWH) who switched to an integrase inhibitor (INSTI)-based regimen. One hundred and fifty-four PWH were included. After 48 weeks, median (Q1–Q3) weight gain was 1.2 (−0.6 to 3.8) kg and median (Q1–Q3) controlled attenuation parameter (CAP) change was −4 (−33 to 27) dB/m. Weight gain was weakly correlated with CAP change [R2 95% confidence interval (CI) = 0.144 (−0.014 to 0.296); P = 0.074)]. Changes in hepatic steatosis after switching to INSTI-based regimens do not seem to parallel weight gain after 1 year.

Published
2023

21. A metagenome-wide association study of HIV disease progression in HIV controllers

Author

Junta de Andalucía, Instituto de Salud Carlos III, European Commission, Consejo Superior de Investigaciones Científicas (España), Real, Luis Miguel, Sáez, María Eugenia, Corma-Gómez, Anaïs, González-Pérez, Antonio, Thorball, Christian, Ruiz, Rocío, Jiménez-León, María Reyes, González-Serna, Alejandro, Gasca-Capote, Carmen, Bravo, María José, Royo, José Luis, Pérez-Gómez, Alberto, Camacho-Sojo, María Inés, Gallego, Isabel, Vitallé, Joana, Bachiller, Sara, Gutiérrez Valencia, Alicia, Vidal, Francisco, Fellay, Jacques, Lichterfeld, Mathias, Ruiz-Mateos, Ezequiel, Swiss HIV Cohort Study, Junta de Andalucía, Instituto de Salud Carlos III, European Commission, Consejo Superior de Investigaciones Científicas (España), Real, Luis Miguel, Sáez, María Eugenia, Corma-Gómez, Anaïs, González-Pérez, Antonio, Thorball, Christian, Ruiz, Rocío, Jiménez-León, María Reyes, González-Serna, Alejandro, Gasca-Capote, Carmen, Bravo, María José, Royo, José Luis, Pérez-Gómez, Alberto, Camacho-Sojo, María Inés, Gallego, Isabel, Vitallé, Joana, Bachiller, Sara, Gutiérrez Valencia, Alicia, Vidal, Francisco, Fellay, Jacques, Lichterfeld, Mathias, Ruiz-Mateos, Ezequiel, and Swiss HIV Cohort Study

Abstract

[Summary] Some HIV controllers experience immunologic progression with CD4+ T cell decline. We aimed to identify genetic factors associated with CD4+ T cell lost in HIV controllers. A total of 561 HIV controllers were included, 442 and 119 from the International HIV controllers Study Cohort and the Swiss HIV Cohort Study, respectively. No SNP or gene was associated with the long-term non-progressor HIV spontaneous control phenotype in the individual GWAS or in the meta-analysis. However, SNPs previously associated with natural HIV control linked to HLA-B (rs2395029 [p = 0.005; OR = 1.70], rs59440261 [p = 0.003; OR = 1.78]), MICA (rs112243036 [p = 0.011; OR = 1.45]), and PSORS1C1 loci (rs3815087 [p = 0.017; OR = 1.39]) showed nominal association with this phenotype. Genetic factors associated with the long-term HIV controllers without risk of immunologic progression are those previously related to the overall HIV controller phenotype.

Published
2023

22. Hepatic Steatosis and Weight Gain During the Coronavirus Disease 2019 Pandemic Among People With Human Immunodeficiency Virus: Impact of Therapy With Tenofovir Alafenamide

Author

Instituto de Salud Carlos III, European Commission, Centros de Investigación Biomédica en Red (España), Ministerio de Ciencia e Innovación (España), Junta de Andalucía, Santos, Marta, Corma-Gómez, Anaïs, Martín-Carmona, Jesica, Pérez-García, Margarita, Martín-Sierra, Carmen, Rincón, Pilar, González-Serna, Alejandro, Pineda, Juan A., Real, Luis Miguel, Macías, Juan, Instituto de Salud Carlos III, European Commission, Centros de Investigación Biomédica en Red (España), Ministerio de Ciencia e Innovación (España), Junta de Andalucía, Santos, Marta, Corma-Gómez, Anaïs, Martín-Carmona, Jesica, Pérez-García, Margarita, Martín-Sierra, Carmen, Rincón, Pilar, González-Serna, Alejandro, Pineda, Juan A., Real, Luis Miguel, and Macías, Juan

Abstract

[Background] Lockdown due to the coronavirus disease 2019 (COVID-19) pandemic led to increases in weight in part of the population. Weight gain leads to hepatic steatosis (HS). Antiretroviral treatment could also influence HS in people with human immunodeficiency virus (PWH). The impact of lockdown on HS in PWH is unknown. The aim of this study was to analyze the changes in HS, as measured by the controlled attenuation parameter (CAP), during the COVID-19 pandemic in PWH., [Methods] This was a cohort study that included PWH who attended a tertiary care center in southern Spain from January 2018 to December 2021. The CAP was evaluated by transient elastography. Only those who had a valid CAP before and after March 2020 were included. HS was defined as CAP ≥248 dB/m., [Results] Six hundred eighty PWH were attended and 488 (71.8%) were included. Two hundred and fourteen (43.9%) had HS at baseline and 239 (49%) at the end of the follow-up (P = .036). The median change in CAP among PWH taking tenofovir alafenamide (TAF) was 8.5 (interquartile range [IQR], −24 to 46.3) dB/m versus −4 (IQR, −35 to 27) dB/m among PWH receiving TAF-free regimens (P = .003). After multivariate analysis, adjusted by sex and age, weight gain (adjusted odds ratio [AOR], 1.09 [95% confidence interval {CI}, 1.05–1.14]; P < .001), TAF therapy (AOR, 1.59 [95% CI, 1.07–2.35]; P = .021), plasma triglycerides (AOR, 1.01 [95% CI, 1–1.01]; P < .001), and fasting blood glucose (AOR, 1.01 [95% CI, 1–1.02]; P = .027) were associated with HS at the end of follow-up., [Conclusions] The frequency of HS increased during the COVID-19 pandemic among PWH. TAF is associated with HS development, regardless of metabolic factors.

Published
2023

23. Hepatic Steatosis and Weight Gain During the Coronavirus Disease 2019 Pandemic Among People With Human Immunodeficiency Virus: Impact of Therapy With Tenofovir Alafenamide

Author

Universidad de Sevilla. Departamento de Fisiología, Instituto de Salud Carlos III, Fondos Europeos FEDER, Santos, Marta, Corma Gómez, Anaïs, Martin Carmona, Jesica, Perez Garcia, Margarita, Martin Sierra, Carmen, Rincón Mayo, Pilar, González Serna, Alejandro, Pineda, Juan Antonio, Real, Luis Miguel, Macias, Juan, Universidad de Sevilla. Departamento de Fisiología, Instituto de Salud Carlos III, Fondos Europeos FEDER, Santos, Marta, Corma Gómez, Anaïs, Martin Carmona, Jesica, Perez Garcia, Margarita, Martin Sierra, Carmen, Rincón Mayo, Pilar, González Serna, Alejandro, Pineda, Juan Antonio, Real, Luis Miguel, and Macias, Juan

Abstract

Lockdown due to the coronavirus disease 2019 (COVID-19) pandemic led to increases in weight in part of the population. Weight gain leads to hepatic steatosis (HS). Antiretroviral treatment could also influence HS in people with human immunodeficiency virus (PWH). The impact of lockdown on HS in PWH is unknown. The aim of this study was to analyze the changes in HS, as measured by the controlled attenuation parameter (CAP), during the COVID-19 pandemic in PWH.

Published
2023

24. Response to glecaprevir/pibrentasvir in HIV/HCV-coinfected patients in clinical practice

Author

Universidad de Sevilla. Departamento de Fisiología, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (MICINN). España, European Commission. Fondo Social Europeo (FSO), Centro de Investigación Biomédica en Red, Fundación para la Investigación en salud (FIS) del Instituto Carlos III, González-Serna Martín, Manuel Alejandro, Corma Gómez, Anaïs, Tellez, Francisco, Ríos Villegas, MJ, Corona Mata, D, Merino, D, Real Navarrete, Luis Miguel, Macías Sánchez, Juan, Universidad de Sevilla. Departamento de Fisiología, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (MICINN). España, European Commission. Fondo Social Europeo (FSO), Centro de Investigación Biomédica en Red, Fundación para la Investigación en salud (FIS) del Instituto Carlos III, González-Serna Martín, Manuel Alejandro, Corma Gómez, Anaïs, Tellez, Francisco, Ríos Villegas, MJ, Corona Mata, D, Merino, D, Real Navarrete, Luis Miguel, and Macías Sánchez, Juan

Abstract

HIV infection has been associated with lower rates of sustained viral response (SVR) with direct-acting antivirals (DAAs). There are few data on glecaprevir/pibrentasvir (G/P) in HIV/HCV coinfection outside clinical trials.

Published
2023

25. HIV infection does not increase the risk of liver complications in hepatitis C virus-infected patient with advanced fibrosis, after sustained virological response with direct-acting antivirals

Author

Corma-Gómez, Anaïs, Morano, Luis, Téllez, Francisco, Rivero-Juárez, Antonio, Real, Luis M., Alados, Juan Carlos, Ríos-Villegas, María José, Vera-Méndez, Francisco Jesús, Muñoz, Rosario Palacios, Geijo, Paloma, Macías, Juan, and Pineda, Juan A.

Published
2019
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27. High efficacy of glecaprevir/pibrentasvir for HCV-infected individuals with active drug use

Author

Universidad de Sevilla. Departamento de Fisiología, Universidad de Sevilla. Departamento de Medicina, Instituto de Salud Carlos III, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Ministerio de Ciencia, Innovación y Universidades (MICINN). España, Servicio Andaluz de Salud, González-Serna Martín, Manuel Alejandro, Macías Sánchez, Juan, Corma Gómez, Anaïs, Tellez, Francisco, Cucurull, Josep, Real Navarrete, Luis Miguel, Granados, Rafael, Rivero Juárez, Antonio, Hernández Quero, José, Merino, Dolores, Palacios, Rosario, Ríos-Villegas, María José, Collado, Antonio, Pineda Vergara, Juan Antonio, Universidad de Sevilla. Departamento de Fisiología, Universidad de Sevilla. Departamento de Medicina, Instituto de Salud Carlos III, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Ministerio de Ciencia, Innovación y Universidades (MICINN). España, Servicio Andaluz de Salud, González-Serna Martín, Manuel Alejandro, Macías Sánchez, Juan, Corma Gómez, Anaïs, Tellez, Francisco, Cucurull, Josep, Real Navarrete, Luis Miguel, Granados, Rafael, Rivero Juárez, Antonio, Hernández Quero, José, Merino, Dolores, Palacios, Rosario, Ríos-Villegas, María José, Collado, Antonio, and Pineda Vergara, Juan Antonio

Abstract

Objectives Real world data on glecaprevir/pibrentasvir (G/P) among active drug users are scarce. We evaluated the sustained virological response (SVR) rates of G/P among individuals with and without active drug use in routine clinical practice. Methods Two ongoing prospective multicenter cohorts of individuals starting G/P were analyzed. Overall SVR intention-to-treat (ITT), discontinuations due to adverse effects and dropouts were evaluated. Results in patients with active, past and without active drug use were compared. Results Overall, 644 individuals started G/P and have reached the date of SVR evaluation. Of them, 613 (95.2%) individuals achieved SVR. There were two (0.3%) relapses, one (0.2%) discontinuation due to side effects and 35 (5.4%) dropouts. SVR rates for patients with active drug use, past drug use and those who never used drugs were 85.4%(n/N = 70/82), 96.1%(n/N = 320/333) and 97.4%(n/N = 223/229) respectively (p < 0.001). After adjustment by sex, age, HCV genotype and opioid agonist therapy, active drug use was the only factor independently associated with SVR (ITT) [adjusted OR (95%confidence interval): 0.29(0.09–0.99),p = 0.048]. Conclusions Active drug use was independently associated with lower SVR rates to G/P, mainly due to voluntary dropout. G/P could be particularly beneficial in this scenario but specific strategies designed to increase the retention in care are needed.

Published
2022

28. Controlled attenuation parameter-insulin resistance (CIR) score to predict non-alcoholic steatohepatitis

Author

Universidad de Sevilla. Departamento de Medicina, Universidad de Sevilla. Departamento de Cirugía, Universidad de Sevilla. Departamento de Fisiología, Consejería de Salud y Familias. Junta de Andalucía, Instituto de Salud Carlos III, Servicio Andaluz de Salud, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Macías Sánchez, Juan, Parra Membrives, Pablo, Sosa Moreno, Francisco, Rincón, Pilar, Martínez Baena, Darío, Fernández Fuertes, Marta, Lorente Herce, José Manuel, Martínez, Rafael C., Jiménez Riera, Águeda Granada, Corma Gómez, Anaïs, González-Serna Martín, Manuel Alejandro, Pineda Vergara, Juan Antonio, Real, Luis Miguel, Universidad de Sevilla. Departamento de Medicina, Universidad de Sevilla. Departamento de Cirugía, Universidad de Sevilla. Departamento de Fisiología, Consejería de Salud y Familias. Junta de Andalucía, Instituto de Salud Carlos III, Servicio Andaluz de Salud, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Macías Sánchez, Juan, Parra Membrives, Pablo, Sosa Moreno, Francisco, Rincón, Pilar, Martínez Baena, Darío, Fernández Fuertes, Marta, Lorente Herce, José Manuel, Martínez, Rafael C., Jiménez Riera, Águeda Granada, Corma Gómez, Anaïs, González-Serna Martín, Manuel Alejandro, Pineda Vergara, Juan Antonio, and Real, Luis Miguel

Abstract

The diagnosis of non-alcoholic steatohepatitis (NASH) requires liver biopsy. Patients with NASH are at risk of progression to advanced fibrosis and hepatocellular carcinoma. A reliable non-invasive tool for the detection of NASH is needed. We aimed at developing a tool to diagnose NASH based on a predictive model including routine clinical and transient hepatic elastography (TE) data. All subjects undergoing elective cholecystectomy in our center were invited to participate, if alcohol intake was < 30 g/d for men and < 15 g/d for women. TE with controlled attenuation parameter (CAP) was obtained before surgery. A liver biopsy was taken during surgery. Multivariate logistic regression models to predict NASH were constructed with the first 100 patients, the elaboration group, and the results were validated in the next pre-planned 50 patients. Overall, 155 patients underwent liver biopsy. In the elaboration group, independent predictors of NASH were CAP value [adjusted OR (AOR) 1.024, 95% confidence interval (95% CI) 1.002–1.046, p = 0.030] and HOMA value (AOR 1.847, 95% CI 1.203–2.835, p < 0.001). An index derived from the logistic regression equation to identify NASH was designated as the CAP-insulin resistance (CIR) score. The area under the receiver operating characteristic curve (95%CI) of the CIR score was 0.93 (0.87–0.99). Positive (PPV) and negative predictive values (NPV) of the CIR score were 82% and 91%, respectively. In the validation set, PPV was 83% and NPV was 88%. In conclusion, the CIR score, a simple index based on CAP and HOMA, can reliably identify patients with and without NASH.

Published
2022

29. High efficacy of glecaprevir/pibrentasvir for HCV-infected individuals with active drug use

Author

Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Junta de Andalucía, Real, Luis Miguel [0000-0003-4932-7429], Rivero-Juárez, Antonio [0000-0002-5813-6889], González, Alejandro, Macías, Juan, Corma-Gómez, Anaïs, Téllez, Francisco, Cucurull, Josep, Real, Luis Miguel, Granados, Rafael, Rivero-Juárez, Antonio, Hernandez-Quero, José, Merino, Dolores, Palacios, Rosario, Ríos-Villegas, María José, Collado, Antonio, Pineda, Juan A., Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Junta de Andalucía, Real, Luis Miguel [0000-0003-4932-7429], Rivero-Juárez, Antonio [0000-0002-5813-6889], González, Alejandro, Macías, Juan, Corma-Gómez, Anaïs, Téllez, Francisco, Cucurull, Josep, Real, Luis Miguel, Granados, Rafael, Rivero-Juárez, Antonio, Hernandez-Quero, José, Merino, Dolores, Palacios, Rosario, Ríos-Villegas, María José, Collado, Antonio, and Pineda, Juan A.

Abstract

[Objectives] Real world data on glecaprevir/pibrentasvir (G/P) among active drug users are scarce. We evaluated the sustained virological response (SVR) rates of G/P among individuals with and without active drug use in routine clinical practice., [Methods] Two ongoing prospective multicenter cohorts of individuals starting G/P were analyzed. Overall SVR intention-to-treat (ITT), discontinuations due to adverse effects and dropouts were evaluated. Results in patients with active, past and without active drug use were compared., [Results] Overall, 644 individuals started G/P and have reached the date of SVR evaluation. Of them, 613 (95.2%) individuals achieved SVR. There were two (0.3%) relapses, one (0.2%) discontinuation due to side effects and 35 (5.4%) dropouts. SVR rates for patients with active drug use, past drug use and those who never used drugs were 85.4%(n/N = 70/82), 96.1%(n/N = 320/333) and 97.4%(n/N = 223/229) respectively (p < 0.001). After adjustment by sex, age, HCV genotype and opioid agonist therapy, active drug use was the only factor independently associated with SVR (ITT) [adjusted OR (95%confidence interval): 0.29(0.09–0.99),p = 0.048]., [Conclusions] Active drug use was independently associated with lower SVR rates to G/P, mainly due to voluntary dropout. G/P could be particularly beneficial in this scenario but specific strategies designed to increase the retention in care are needed.

Published
2022

30. Controlled attenuation parameter-insulin resistance (CIR) score to predict non-alcoholic steatohepatitis

Author

Junta de Andalucía, Universidad Carlos III de Madrid, European Commission, Macías Sánchez, Juan, Parra-Membrives, Pablo, Sosa-Moreno, Francisco, Rincón, Pilar, Martínez-Baena, Darío, Fernández-Fuertes, Marta, Lorente-Herce, José M., Martínez, Rafael, Jiménez-Riera, Granada, Corma-Gómez, Anaïs, González-Serna, A., Pineda, Juan A., Real, Luis Miguel, Junta de Andalucía, Universidad Carlos III de Madrid, European Commission, Macías Sánchez, Juan, Parra-Membrives, Pablo, Sosa-Moreno, Francisco, Rincón, Pilar, Martínez-Baena, Darío, Fernández-Fuertes, Marta, Lorente-Herce, José M., Martínez, Rafael, Jiménez-Riera, Granada, Corma-Gómez, Anaïs, González-Serna, A., Pineda, Juan A., and Real, Luis Miguel

Abstract

The diagnosis of non-alcoholic steatohepatitis (NASH) requires liver biopsy. Patients with NASH are at risk of progression to advanced fibrosis and hepatocellular carcinoma. A reliable non-invasive tool for the detection of NASH is needed. We aimed at developing a tool to diagnose NASH based on a predictive model including routine clinical and transient hepatic elastography (TE) data. All subjects undergoing elective cholecystectomy in our center were invited to participate, if alcohol intake was < 30 g/d for men and < 15 g/d for women. TE with controlled attenuation parameter (CAP) was obtained before surgery. A liver biopsy was taken during surgery. Multivariate logistic regression models to predict NASH were constructed with the first 100 patients, the elaboration group, and the results were validated in the next pre-planned 50 patients. Overall, 155 patients underwent liver biopsy. In the elaboration group, independent predictors of NASH were CAP value [adjusted OR (AOR) 1.024, 95% confidence interval (95% CI) 1.002-1.046, p = 0.030] and HOMA value (AOR 1.847, 95% CI 1.203-2.835, p < 0.001). An index derived from the logistic regression equation to identify NASH was designated as the CAP-insulin resistance (CIR) score. The area under the receiver operating characteristic curve (95%CI) of the CIR score was 0.93 (0.87-0.99). Positive (PPV) and negative predictive values (NPV) of the CIR score were 82% and 91%, respectively. In the validation set, PPV was 83% and NPV was 88%. In conclusion, the CIR score, a simple index based on CAP and HOMA, can reliably identify patients with and without NASH.

Published
2022

32. Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Author

Rojas, Itziar de, Hernández, Isabel, Montrreal, Laura, Quintela, Inés, Calero, Miguel, Royo, José Luis, Huerto Vilas, Raquel, González-Pérez, Antonio, Franco-Macías, Emilio, Macias, Juan, Menéndez-González, Manuel, Frank-García, Ana, Díez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, Aguilera, Nuria, Garcia-González, Pablo, Puerta, Raquel, Sotolongo-Grau, Oscar, Alonso-Lana, Silvia, Rábano, Alberto, Arias Pastor, Alfonso, Pastor, Ana Belén, Corma-Gómez, Anaïs, Martin Montes, Ángel, Martínez Rodríguez, Carmen, Buiza-Rueda, Dolores, Periñán, María Teresa, Rodríguez-Rodríguez, Eloy, Álvarez, Ignacio, Rosas Allende, Irene, Pineda, Juan A., Bernal Sánchez-Arjona, María, Fernández-Fuertes, Marta, Mendoza, Silvia, Ser, Teodoro del, GR@ACE, DEGESCO Consortium, García-Ribas, Guillermo, Sanchez-Juan, Pascual, Pastor, Pau, Bullido, María Jesús, Álvarez, Victoria, Real, Luis M., Mir, Pablo, Piñol-Ripoll, Gerard, García-Alberca, José María, Medina, Miguel, Orellana, Adelina, Butler, Christopher R., Marquie, Marta, Sáez, María Eugenia, Carracedo, Ángel, Tárraga, Lluís, Boada, Mercè, Ruiz, Agustín, Instituto de Salud Carlos III, Unión Europea, Grifols (Spain), Fundación La Caixa, Fundació ACE, Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas), Fundación Reina Sofía, Grifols, La Caixa, Ace Alzheimer Center Barcelona, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), European Commission, Rojas, Itziar de [0000-0002-2148-381X], Calero, Miguel [0000-0001-5366-3324], Menéndez-González, Manuel [0000-0002-5218-0774], Díez-Fairen, Mónica [0000-0003-1882-0309], Rábano, Alberto [0000-0001-9320-6566], Rodríguez-Rodríguez, Eloy [0000-0001-7742-677X], Álvarez, Ignacio [0000-0002-8537-3935], Bullido, María Jesús [0000-0002-6477-1117], Álvarez, Victoria [0000-0002-1916-2523], Real, Luis M. [0000-0003-4932-7429], Medina, Miguel [0000-0002-7016-5340], Butler, Christopher R. [0000-0002-7502-9284], Sáez, María Eugenia [0000-0001-9299-2534], Carracedo, Ángel [0000-0003-1085-8986], Ruiz, Agustín [0000-0003-2633-2495], Universidad de Cantabria, Rojas, Itziar de, Calero, Miguel, Menéndez-González, Manuel, Díez-Fairen, Mónica, Rábano, Alberto, Rodríguez-Rodríguez, Eloy, Álvarez, Ignacio, Bullido, María Jesús, Álvarez, Victoria, Real, Luis M., Medina, Miguel, Butler, Christopher R., Sáez, María Eugenia, Carracedo, Ángel, Ruiz, Agustín, and UAM. Departamento de Biología Molecular

Subjects
SARS-CoV-2, COVID-19, GWAS, GR@ACE/DEGESCO, dementia, APOE, Medicine (miscellaneous), Biología y Biomedicina / Biología, Article, Medicine
Abstract

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis., We would like to thank patients and controls who participated in this project. The present work has been performed as part of the doctoral program of I. de Rojas at the Universitat de Barcelona (Barcelona, Spain) supported by national grant from the Instituto de Salud Carlos III FI20/00215. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria ‘La Caixa’, Fundació ACE, and CIBERNED. The Vallecas Project is supported by Queen Sofia Foundation and the Instituto de Salud Carlos III. The position held by SA-L is funded by Instituto de Salud Carlos III (Co-funded by European Social Fund “Investing in your future”) Sara Borrell Contract (CD19/00232). A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240 and PI19/01301. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)–Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER–‘Una manera de hacer Europa’). Some control samples and data from patients included in this study were provided in part by the National DNA Bank Carlos III (www.bancoadn.org, accessed date: 1 October 2021, University of Salamanca, Spain) and Hospital Universitario Virgen de Valme (Sevilla, Spain); they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. This research has been conducted using the COVID-19 Host Genetic Initiative public resource obtained through the web site (https://www.covid19hg.org/results/, accessed date: 1 October 2021).

Published
2021

33. A Genome-Wide Association Study on Liver Stiffness Changes during Hepatitis C Virus Infection Cure

Author

Corma-Gómez, Anaïs, primary, Macías, Juan, additional, Rivero, Antonio, additional, Rivero-Juarez, Antonio, additional, de los Santos, Ignacio, additional, Reus-Bañuls, Sergio, additional, Morano, Luis, additional, Merino, Dolores, additional, Palacios, Rosario, additional, Galera, Carlos, additional, Fernández-Fuertes, Marta, additional, González-Serna, Alejandro, additional, de Rojas, Itziar, additional, Ruiz, Agustín, additional, Sáez, María E., additional, Real, Luis M., additional, and Pineda, Juan A., additional

Published
2021
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34. Factores predictores de eventos clínicos tras la respuesta viral sostenida en pacientes con infección crónica por el virus de la hepatitis C y fibrosis hepática avanzada

Author

Corma Gómez, Anaïs, Pineda Vergara, Juan Antonio, Miguel Real, Luis, and Universidad de Sevilla. Departamento de Medicina

Abstract

A pesar de las altas tasas de curación de la infección por el virus de la hepatitis C (VHC) a partir de la reciente introducción de los antivirales de acción directa (AAD), incluso en los escenarios más complicados, la carga de la enfermedad hepática residual a esta infección sigue siendo un importante problema de salud pública. Los factores asociados a una evolución clínica desfavorable son de sobra conocidos en el contexto de la infección por el VHC activa. Sin embargo, la información relativa a la evolución clínica y al manejo adecuado de las complicaciones que pueden surgir tras la respuesta viral sostenida (RVS) de los pacientes al tratamiento erradicador, es limitada. Por ello, la presente Tesis Doctoral se ha centrado en evaluar los factores que se asocian a evolución clínica en este contexto específico de pacientes. Más concretamente, dado que el VIH modifica sustancialmente la historia natural de la enfermedad hepática durante la infección activa por el VHC, es razonable pensar que, tras la consecución de la RVS con AAD siga teniendo un impacto negativo. Por otro lado, a pesar de que la rigidez hepática, evaluada mediante elastografía hepática de transición con vibración controlada (ETVC), ha demostrado ser un potente predictor de eventos clínicos en pacientes con infección activa, su valor predictivo después de la curación no ha sido analizado. Específicamente, un valor de rigidez hepática por debajo de 21 KPa identifica a los individuos cirróticos con bajo riesgo de desarrollar sangrado de varices esofágicas (VE) por hipertensión portal, durante la infección activa por el VHC. Sin embargo, el rendimiento diagnóstico de esta técnica con dicha finalidad no se ha evaluado tras la RVS. El objetivo global de la presente Tesis Doctoral fue por valor predictivo de varios factores en el desarrollo de eventos clínicos después de lograr respuesta viral sostenida en pacientes infectados con fibrosis avanzada previa al tratamiento. Los tres estudios que componen este trabajo se llevaron a cabo en la cohorte GEHEP-011 (clinicaltrials.gov ID: NCT04460157). Se trata de una cohorte multicéntrica en la que participan unidades de Enfermedades Infecciosas de 18 hospitales españoles. En ella se incluyen pacientes monoinfectados por el VHC y coinfectados por el VIH/VHC que cumplen los siguientes criterios: 1) Haber recibido un régimen terapéutico con al menos un AAD, ya fuera libre de IFN o no; 2) Presentar una RH, medida por ETVC, previa al tratamiento ≥9,5 KPa; 3) Haber alcanzado RVS después de la finalización del tratamiento, definida como una PCR negativa para ARN del VHC en sangre en ese momento; y 4) Disponer de una medición de la RH por ETVC válida en el momento de la RVS. Los pacientes con HBsAg sérico positivo son excluidos del estudio. En primer lugar, se evaluó el impacto de la coinfección por VIH sobre el riesgo de desarrollar eventos hepáticos en pacientes con infección crónica por el VHC y fibrosis avanzada, que alcanzan la RVS con regímenes basados en AAD. Este objetivo concreto se abordó en el trabajo “HIV infection does not increase the risk of liver complications in hepatitis C virus-infected patient with advanced fibrosis, after sustained virological response with direct-acting antivirals”. Se puso de manifiesto que, al contrario de lo que ocurre durante la infección por VHC activa, la coinfección por el VIH no tiene un impacto negativo en la progresión de la enfermedad hepática, en estos pacientes tras la curación del VHC. En segundo lugar, se determinó el valor predictivo de la rigidez hepática, medida por ETVC, en el momento de la RVS, para la aparición de complicaciones hepáticas en pacientes con infección por VIH e infección crónica por VHC y fibrosis avanzada previa al tratamiento, tratados con AAD. Este objetivo se cumplió en el trabajo “Liver Stiffness at the time of sustained virological response predicts the clinical outcome in people living with human immunodeficiency virus and hepatitis C virus with advanced fibrosis treated with direct-acting antivirals”. En éste se concluyó que la RH, evaluada por ETVC, en el momento de la curación, fue capaz de identificar por sí sola a aquellos pacientes con un bajo riesgo de desarrollar complicaciones hepáticas tras la RVS. Estos individuos podrían ser potencialmente excluidos de los programas de cribado de complicaciones hepáticas de forma segura, después de la RVS. Además, la RH en RVS también resultó ser un factor predictor de muerte por cualquier causa en estos individuos. Por último, se validaron marcadores basados en la rigidez hepática previamente descritos, medidos en el momento de la RVS, para predecir el sangrado digestivo por varices esofágicas en pacientes con infección crónica por VHC en fase de cirrosis hepática, coinfectados o no por VIH, que alcanzan la RVS con regímenes basados en AAD. Este objetivo se acometió en el trabajo “Liver stiffness-based strategies predict absence of variceal bleeding in cirrhotic HCV-infected patients with and without HIV-coinfection after sustained virological response”. Se demostró que las estrategias de cribado de VE basadas en la RH y validadas durante la infección activa por VHC también presentan un buen rendimiento después de la consecución de la RVS, en pacientes con cirrosis hepática por VHC. Los criterios HEPAVIR, VIH/cirrosis y BAVENO VI expandido evaluados en el momento de la RVS son de gran utilidad para identificar a aquellos individuos cirróticos con bajo riesgo de presentar un sangrado por VE tras la curación de la infección por VHC. Concretamente, el criterio VIH/cirrosis es capaz de identificar al máximo número de pacientes en los que podrían interrumpirse las medidas de vigilancia de VE, sin que se produzcan eventos hemorrágicos en individuos no cribados.

Published
2021

35. Factores predictores de eventos clínicos tras la respuesta viral sostenida en pacientes con infección crónica por el virus de la hepatitis C y fibrosis hepática avanzada

Author

Pineda Vergara, Juan Antonio, Miguel Real, Luis, Universidad de Sevilla. Departamento de Medicina, Corma Gómez, Anaïs, Pineda Vergara, Juan Antonio, Miguel Real, Luis, Universidad de Sevilla. Departamento de Medicina, and Corma Gómez, Anaïs

Abstract

A pesar de las altas tasas de curación de la infección por el virus de la hepatitis C (VHC) a partir de la reciente introducción de los antivirales de acción directa (AAD), incluso en los escenarios más complicados, la carga de la enfermedad hepática residual a esta infección sigue siendo un importante problema de salud pública. Los factores asociados a una evolución clínica desfavorable son de sobra conocidos en el contexto de la infección por el VHC activa. Sin embargo, la información relativa a la evolución clínica y al manejo adecuado de las complicaciones que pueden surgir tras la respuesta viral sostenida (RVS) de los pacientes al tratamiento erradicador, es limitada. Por ello, la presente Tesis Doctoral se ha centrado en evaluar los factores que se asocian a evolución clínica en este contexto específico de pacientes. Más concretamente, dado que el VIH modifica sustancialmente la historia natural de la enfermedad hepática durante la infección activa por el VHC, es razonable pensar que, tras la consecución de la RVS con AAD siga teniendo un impacto negativo. Por otro lado, a pesar de que la rigidez hepática, evaluada mediante elastografía hepática de transición con vibración controlada (ETVC), ha demostrado ser un potente predictor de eventos clínicos en pacientes con infección activa, su valor predictivo después de la curación no ha sido analizado. Específicamente, un valor de rigidez hepática por debajo de 21 KPa identifica a los individuos cirróticos con bajo riesgo de desarrollar sangrado de varices esofágicas (VE) por hipertensión portal, durante la infección activa por el VHC. Sin embargo, el rendimiento diagnóstico de esta técnica con dicha finalidad no se ha evaluado tras la RVS. El objetivo global de la presente Tesis Doctoral fue por valor predictivo de varios factores en el desarrollo de eventos clínicos después de lograr respuesta viral sostenida en pacientes infectados con fibrosis avanzada previa al tratamiento. Los tres estudios que componen este

Published
2021

36. Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Author

Instituto de Salud Carlos III, Grifols, La Caixa, Ace Alzheimer Center Barcelona, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Fundación Reina Sofía, European Commission, Rojas, Itziar de [0000-0002-2148-381X], Calero, Miguel [0000-0001-5366-3324], Menéndez-González, Manuel [0000-0002-5218-0774], Díez-Fairen, Mónica [0000-0003-1882-0309], Rábano, Alberto [0000-0001-9320-6566], Rodríguez-Rodríguez, Eloy [0000-0001-7742-677X], Álvarez, Ignacio [0000-0002-8537-3935], Bullido, María Jesús [0000-0002-6477-1117], Álvarez, Victoria [0000-0002-1916-2523], Real, Luis M. [0000-0003-4932-7429], Medina, Miguel [0000-0002-7016-5340], Butler, Christopher R. [0000-0002-7502-9284], Sáez, María Eugenia [0000-0001-9299-2534], Carracedo, Ángel [0000-0003-1085-8986], Ruiz, Agustín [0000-0003-2633-2495], Rojas, Itziar de, Hernández, Isabel, Montrreal, Laura, Quintela, Inés, Calero, Miguel, Royo, José Luis, Huerto Vilas, Raquel, González-Pérez, Antonio, Franco-Macías, Emilio, Macías Sánchez, Juan, Menéndez-González, Manuel, Frank-García, Ana, Díez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, Aguilera, Nuria, García-González, Pablo, Puerta, Raquel, Sotolongo-Grau, Oscar, Alonso-Lana, Silvia, Rábano, Alberto, Arias Pastor, Alfonso, Pastor, Ana Belén, Corma-Gómez, Anaïs, Martin Montes, Ángel, Martínez Rodríguez, Carmen, Buiza-Rueda, Dolores, Periñán, María Teresa, Rodríguez-Rodríguez, Eloy, Álvarez, Ignacio, Rosas Allende, Irene, Pineda, Juan A., Bernal Sánchez-Arjona, María, Fernández-Fuertes, Marta, Mendoza, Silvia, Ser, Teodoro del, GR@ACE, DEGESCO Consortium, García-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Bullido, María Jesús, Álvarez, Victoria, Real, Luis Miguel, Mir, Pablo, Piñol-Ripoll, Gerard, García-Alberca, José María, Medina, Miguel, Orellana, Adelina, Butler, Christopher R., Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Tárraga, Lluís, Boada, Mercè, Ruiz, Agustín, Instituto de Salud Carlos III, Grifols, La Caixa, Ace Alzheimer Center Barcelona, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Fundación Reina Sofía, European Commission, Rojas, Itziar de [0000-0002-2148-381X], Calero, Miguel [0000-0001-5366-3324], Menéndez-González, Manuel [0000-0002-5218-0774], Díez-Fairen, Mónica [0000-0003-1882-0309], Rábano, Alberto [0000-0001-9320-6566], Rodríguez-Rodríguez, Eloy [0000-0001-7742-677X], Álvarez, Ignacio [0000-0002-8537-3935], Bullido, María Jesús [0000-0002-6477-1117], Álvarez, Victoria [0000-0002-1916-2523], Real, Luis M. [0000-0003-4932-7429], Medina, Miguel [0000-0002-7016-5340], Butler, Christopher R. [0000-0002-7502-9284], Sáez, María Eugenia [0000-0001-9299-2534], Carracedo, Ángel [0000-0003-1085-8986], Ruiz, Agustín [0000-0003-2633-2495], Rojas, Itziar de, Hernández, Isabel, Montrreal, Laura, Quintela, Inés, Calero, Miguel, Royo, José Luis, Huerto Vilas, Raquel, González-Pérez, Antonio, Franco-Macías, Emilio, Macías Sánchez, Juan, Menéndez-González, Manuel, Frank-García, Ana, Díez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, Aguilera, Nuria, García-González, Pablo, Puerta, Raquel, Sotolongo-Grau, Oscar, Alonso-Lana, Silvia, Rábano, Alberto, Arias Pastor, Alfonso, Pastor, Ana Belén, Corma-Gómez, Anaïs, Martin Montes, Ángel, Martínez Rodríguez, Carmen, Buiza-Rueda, Dolores, Periñán, María Teresa, Rodríguez-Rodríguez, Eloy, Álvarez, Ignacio, Rosas Allende, Irene, Pineda, Juan A., Bernal Sánchez-Arjona, María, Fernández-Fuertes, Marta, Mendoza, Silvia, Ser, Teodoro del, GR@ACE, DEGESCO Consortium, García-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Bullido, María Jesús, Álvarez, Victoria, Real, Luis Miguel, Mir, Pablo, Piñol-Ripoll, Gerard, García-Alberca, José María, Medina, Miguel, Orellana, Adelina, Butler, Christopher R., Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Tárraga, Lluís, Boada, Mercè, and Ruiz, Agustín

Abstract

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis.

Published
2021

37. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Author

Instituto de Salud Carlos III, Grifols, La Caixa, European Research Council, Pérez-Tur, Jordi [0000-0002-9111-1712], Rojas, Itziar de, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, N. L., Stringa, N., Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Rossi, Giacomina, Tankard, R. M., Wiltfang, J., Giegling, Ina, Seidu, N. M., Dalmasso, Maria Carolina, Benussi, A., Boschi, Silvia, Sáez, María Eugenia, Binetti, Giuliano, Royo, José Luis, Pérez-Tur, Jordi, Spalletta, Gianfranco, Corbaton-Anchuelo, A., Froelich, L., Satizabal, Claudia L., Hagg, S., Ortega, G., Peters, Oliver, Vogelgsang, Jonathan, Serrano-Rios, M., Gil, S., Djurovic, Srdjan, Van Dongen, Jasper, Deramecourt, V., Kalaria, R. N., Wang, L. S., Goldhardt, O., Charbonnier, Camille, Farotti, Lucia, Kornhuber, Johannes, Andreassen, Ole A., Álvarez, Victoria, Herrmann, Martin J., Pasquier, Florence, Calero, Miguel, Holmes, Clive, Haapasalo, Annakaisa, Scherbaum, Norbert, Scheltens, Philip, Caffarra, P., Pineda, Juan A., Del Ser, Teodoro, Hort, Jakub, Espinosa, A., Bullido, María Jesús, Hampel, Harald, Medina, Miguel, Williams, Julie, Sims, Rebecca, Martinez-Larrad, M. T., Riederer, Peter, Esiri, M., Botne Sando, S., Grunblatt, E., Hoffmann, Per, Hiltunen, Mikko, Kern, Silke, Mendoza, Silvia, Kilander, Lena, Jessen, F., Ghidoni, R., Giedraitis, Vilmantas, Molina-Porcel, Laura, Sánchez-Juan, Pascual, Schmid, Matthias, van Duijn, Cornelia M., Antonell, A., Mir, Pablo, Moreno, F., Ferreira, Catarina B., Skrobot, Olivia, Sanchez-Valle, R., Chene, G., Duron, Emmanuelle, Martin Montes, Ángel, Ciccone, Simona, Piñol-Ripoll, Gerard, Ngandu, Tiia, Dardiotis, Efthimios, Scherer, Martin, Arosio, Beatrice, Meggy, A., Sotolongo-Grau, Oscar, Selbaek, Geir, Aarsland, D., Seshadri, Sudha, Bailly, Henri, Sánchez-García, Florentino, Roberto, Natalia, Armstrong, Nicola J., Farrer, Lindsay A., Popp, Julius, Riedel-Heller, Steffi, Fernández-Fuertes, Marta, Scamosci, Michela, Alcolea, Daniel, Rosas Allende, Irene, Marquié, Marta, Benussi, Luisa, Ewers, Michael, Antúnez, Carmen, van Broeckhoven, Christine, Masullo, C., Vyhnalek, Martin, Bossu, Paola, Appollonio, I., Mayeux, R., Lerch, Ondrej, Rábano, Alberto, Quenez, Olivier, Schneider, Anja, Wallon, David, Macías Sánchez, Juan, PGC-ALZ consortia, Yang, Q., Helisalmi, Seppo, Huisman, M., Lambert, Jean-Charles, Kehoe, Patrick G., Heneka, Michael T., DEGESCO consortium, Papenberg, Goran, Lowenmark, M., Frikke-Schmidt, Ruth, Fornage, Myriam, Kunkle, Brian W., Heilmann-Heimbach, Stefanie, Posthuma, Danielle, Tremolizzo, Lucio, Amouyel, Philippe, Franco-Macías, Emilio, Munoz-Fernandez, C., Sorbi, Sandro, Küçükali, Fahri, Dionigi Rossi, P., Huerto Vilas, Raquel, Spallazzi, Marco, Alarcón-Martín, Emilio, Maier, Wolfgang, de Mendonça, Alexandre, The GR@ACE study group, Benaque, Alba, EADB contributors, IGAP (ADGC, CHARGE, EADI, GERAD), van der Lee, Sven J., DeStefano, Anita, Lleó, Alberto, Kosmidis, Mary H., Rongve, A., Nicolas, Gael, Escott-Price, Valentina, Tybjaerg-Hansen, Anne, Chillotti, Caterina, Pastor, Pau, Buiza-Rueda, Dolores, Alegret, Montserrat, Lage, Carmen, Holmans, Peter A., Polak, Thomas, Pastor, Ana Belén, Nöthen, Markus M., García-Ribas, Guillermo, Pijnenburg, Yolande A L, Vidal, Jean-Sebastien, Squassina, Alessio, Kuulasmaa, Teemu, Pericak-Vance, M. A., Pisanu, Claudia, Fliessbach, Klaus, Grimmer, Timo, Galimberti, Daniela, Parnetti, L., López de Munain, Adolfo, Soininen, Hilkka, Carracedo, Ángel, Deckert, Jurgen, Karlsson, I. K., Buerger, Katharina, Clark, Christopher, Cecchetti, Roberta, Fostinelli, Silvia, Deniz-Naranjo, M. C., Engelborghs, S., Álvarez, Ignacio, Sakka, Paraskevi, Thomassen, Jesper Qvist, Ramirez, A., Holstege, Henne, Marshall, Rachel, Haines, Jonathan L., Hulsman, Marc, Kleineidam, Luca, Ferri, E., Pérez-Cordon, Alba, Menéndez-González, Manuel, van der Flier, Wiesje M., Rainero, Innocenzo, Rujescu, D., Wagner, Michael, Corma-Gómez, Anaïs, Lebouvier, T., Ruiz, Agustín, Vandenberghe, Rik, Weinhold, Leonie, Padovani, Alessandro, Diehl-Schmid, Janine, Mead, Simon, Fenoglio, Chiara, Conti, Elisa, Díez-Fairen, Mónica, Fischer, Peter, Abdelnour, Carla, Giaccone, G., González-Pérez, Antonio, Hartmann, Annette M., Hadjigeorgiou, Georgios, Zulaica, M., Sleegers, Kristel, Martínez Rodríguez, Carmen, García-González, Pablo, Rubino, Elisa, Bis, Joshua C., Orellana, Adelina, Zetterberg, Henrik, Schellenberg, Gerard D., Borroni, Barbara, Sanabria, Angela, Fortea, J., Reynolds, C. A., Gelpi, E., Bernal Sánchez-Arjona, María, Boerwinkle, Eric, Mather, K. A., Jian, X., Saltvedt, Ingvild, Frank-García, Ana, Rosende-Roca, Maitee, Kinhult Stahlbom, Anne, Hanon, Olivier, Skoog, Ingmar, Kivipelto, Miia, Lehtisalo, Jenni, García-Alberca, José María, Dufouil, Carole, Bellenguez, Celine, Ingelsson, Martin, Nacmias, B., Spottke, Annika, Ullgren, Abbe, Hausner, Lucrezia, Arias Pastor, Alfonso, Tsolaki, Magda, Seripa, Davide, Naj, A. C., Clarimón, Jordi, Nordestgaard, Borge G., Valero, Sergi, van Schoor, N. M., Scarpini, E., Graff, Caroline, Boada, Mercè, Tagliavini, F., Scarmeas, N., García-Madrona, Sebastián, Yannakoulia, Mary, Banaj, Nerisa, Blennow, Kaj, Duzel, Emrah, Tárraga, Lluís, Lemstra, A. W., Morgan, K., Kok, A. A. L., Bessi, Valentina, Baquero, Miquel, Rodríguez-Rodríguez, Eloy, Cervera-Carles, Laura, Archetti, Silvana, Grande, Giulia, Dichgans, Martin, Arcaro, Marina, Blesa, Rafael, Real, Luis Miguel, Ikram, M. Arfan, Mangialasche, Francesca, Quintela, Inés, Instituto de Salud Carlos III, Grifols, La Caixa, European Research Council, Pérez-Tur, Jordi [0000-0002-9111-1712], Rojas, Itziar de, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, N. L., Stringa, N., Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Rossi, Giacomina, Tankard, R. M., Wiltfang, J., Giegling, Ina, Seidu, N. M., Dalmasso, Maria Carolina, Benussi, A., Boschi, Silvia, Sáez, María Eugenia, Binetti, Giuliano, Royo, José Luis, Pérez-Tur, Jordi, Spalletta, Gianfranco, Corbaton-Anchuelo, A., Froelich, L., Satizabal, Claudia L., Hagg, S., Ortega, G., Peters, Oliver, Vogelgsang, Jonathan, Serrano-Rios, M., Gil, S., Djurovic, Srdjan, Van Dongen, Jasper, Deramecourt, V., Kalaria, R. N., Wang, L. S., Goldhardt, O., Charbonnier, Camille, Farotti, Lucia, Kornhuber, Johannes, Andreassen, Ole A., Álvarez, Victoria, Herrmann, Martin J., Pasquier, Florence, Calero, Miguel, Holmes, Clive, Haapasalo, Annakaisa, Scherbaum, Norbert, Scheltens, Philip, Caffarra, P., Pineda, Juan A., Del Ser, Teodoro, Hort, Jakub, Espinosa, A., Bullido, María Jesús, Hampel, Harald, Medina, Miguel, Williams, Julie, Sims, Rebecca, Martinez-Larrad, M. T., Riederer, Peter, Esiri, M., Botne Sando, S., Grunblatt, E., Hoffmann, Per, Hiltunen, Mikko, Kern, Silke, Mendoza, Silvia, Kilander, Lena, Jessen, F., Ghidoni, R., Giedraitis, Vilmantas, Molina-Porcel, Laura, Sánchez-Juan, Pascual, Schmid, Matthias, van Duijn, Cornelia M., Antonell, A., Mir, Pablo, Moreno, F., Ferreira, Catarina B., Skrobot, Olivia, Sanchez-Valle, R., Chene, G., Duron, Emmanuelle, Martin Montes, Ángel, Ciccone, Simona, Piñol-Ripoll, Gerard, Ngandu, Tiia, Dardiotis, Efthimios, Scherer, Martin, Arosio, Beatrice, Meggy, A., Sotolongo-Grau, Oscar, Selbaek, Geir, Aarsland, D., Seshadri, Sudha, Bailly, Henri, Sánchez-García, Florentino, Roberto, Natalia, Armstrong, Nicola J., Farrer, Lindsay A., Popp, Julius, Riedel-Heller, Steffi, Fernández-Fuertes, Marta, Scamosci, Michela, Alcolea, Daniel, Rosas Allende, Irene, Marquié, Marta, Benussi, Luisa, Ewers, Michael, Antúnez, Carmen, van Broeckhoven, Christine, Masullo, C., Vyhnalek, Martin, Bossu, Paola, Appollonio, I., Mayeux, R., Lerch, Ondrej, Rábano, Alberto, Quenez, Olivier, Schneider, Anja, Wallon, David, Macías Sánchez, Juan, PGC-ALZ consortia, Yang, Q., Helisalmi, Seppo, Huisman, M., Lambert, Jean-Charles, Kehoe, Patrick G., Heneka, Michael T., DEGESCO consortium, Papenberg, Goran, Lowenmark, M., Frikke-Schmidt, Ruth, Fornage, Myriam, Kunkle, Brian W., Heilmann-Heimbach, Stefanie, Posthuma, Danielle, Tremolizzo, Lucio, Amouyel, Philippe, Franco-Macías, Emilio, Munoz-Fernandez, C., Sorbi, Sandro, Küçükali, Fahri, Dionigi Rossi, P., Huerto Vilas, Raquel, Spallazzi, Marco, Alarcón-Martín, Emilio, Maier, Wolfgang, de Mendonça, Alexandre, The GR@ACE study group, Benaque, Alba, EADB contributors, IGAP (ADGC, CHARGE, EADI, GERAD), van der Lee, Sven J., DeStefano, Anita, Lleó, Alberto, Kosmidis, Mary H., Rongve, A., Nicolas, Gael, Escott-Price, Valentina, Tybjaerg-Hansen, Anne, Chillotti, Caterina, Pastor, Pau, Buiza-Rueda, Dolores, Alegret, Montserrat, Lage, Carmen, Holmans, Peter A., Polak, Thomas, Pastor, Ana Belén, Nöthen, Markus M., García-Ribas, Guillermo, Pijnenburg, Yolande A L, Vidal, Jean-Sebastien, Squassina, Alessio, Kuulasmaa, Teemu, Pericak-Vance, M. A., Pisanu, Claudia, Fliessbach, Klaus, Grimmer, Timo, Galimberti, Daniela, Parnetti, L., López de Munain, Adolfo, Soininen, Hilkka, Carracedo, Ángel, Deckert, Jurgen, Karlsson, I. K., Buerger, Katharina, Clark, Christopher, Cecchetti, Roberta, Fostinelli, Silvia, Deniz-Naranjo, M. C., Engelborghs, S., Álvarez, Ignacio, Sakka, Paraskevi, Thomassen, Jesper Qvist, Ramirez, A., Holstege, Henne, Marshall, Rachel, Haines, Jonathan L., Hulsman, Marc, Kleineidam, Luca, Ferri, E., Pérez-Cordon, Alba, Menéndez-González, Manuel, van der Flier, Wiesje M., Rainero, Innocenzo, Rujescu, D., Wagner, Michael, Corma-Gómez, Anaïs, Lebouvier, T., Ruiz, Agustín, Vandenberghe, Rik, Weinhold, Leonie, Padovani, Alessandro, Diehl-Schmid, Janine, Mead, Simon, Fenoglio, Chiara, Conti, Elisa, Díez-Fairen, Mónica, Fischer, Peter, Abdelnour, Carla, Giaccone, G., González-Pérez, Antonio, Hartmann, Annette M., Hadjigeorgiou, Georgios, Zulaica, M., Sleegers, Kristel, Martínez Rodríguez, Carmen, García-González, Pablo, Rubino, Elisa, Bis, Joshua C., Orellana, Adelina, Zetterberg, Henrik, Schellenberg, Gerard D., Borroni, Barbara, Sanabria, Angela, Fortea, J., Reynolds, C. A., Gelpi, E., Bernal Sánchez-Arjona, María, Boerwinkle, Eric, Mather, K. A., Jian, X., Saltvedt, Ingvild, Frank-García, Ana, Rosende-Roca, Maitee, Kinhult Stahlbom, Anne, Hanon, Olivier, Skoog, Ingmar, Kivipelto, Miia, Lehtisalo, Jenni, García-Alberca, José María, Dufouil, Carole, Bellenguez, Celine, Ingelsson, Martin, Nacmias, B., Spottke, Annika, Ullgren, Abbe, Hausner, Lucrezia, Arias Pastor, Alfonso, Tsolaki, Magda, Seripa, Davide, Naj, A. C., Clarimón, Jordi, Nordestgaard, Borge G., Valero, Sergi, van Schoor, N. M., Scarpini, E., Graff, Caroline, Boada, Mercè, Tagliavini, F., Scarmeas, N., García-Madrona, Sebastián, Yannakoulia, Mary, Banaj, Nerisa, Blennow, Kaj, Duzel, Emrah, Tárraga, Lluís, Lemstra, A. W., Morgan, K., Kok, A. A. L., Bessi, Valentina, Baquero, Miquel, Rodríguez-Rodríguez, Eloy, Cervera-Carles, Laura, Archetti, Silvana, Grande, Giulia, Dichgans, Martin, Arcaro, Marina, Blesa, Rafael, Real, Luis Miguel, Ikram, M. Arfan, Mangialasche, Francesca, and Quintela, Inés

Abstract

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.

Published
2021

38. Liver stiffness at the time of sustained virological response predicts the clinical outcome in HIV/HCV-coinfected patients with advanced fibrosis treated with direct-acting antivirals

Author

Corma-Gómez, Anaïs, Macias, Juan, Téllez, Francisco, Freyre-Carrillo, C., Morano-Amado, Luis E., Rivero-Juárez, Antonio, Ríos-Villegas, María José, Alados, Juan Carlos, Vera-Méndez, Francisco Jesús, Merchante, Nicolás, Palacios, Rosario, Granados, Rafael, Merino, Dolores, De Los Santos, Ignacio, Pineda, Juan A., Instituto de Salud Carlos III, European Commission, Red Española de Investigación en SIDA, and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica

Subjects
Cirrhosis, Hepatocellular carcinoma, virus diseases, Response, Direct-acting antivirals, HIV/HCV coinfection, Sustained, Virological, digestive system diseases
Abstract

On behalf of RIS-HEP13 and GEHEP 011 study groups. In Press., [Background] Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). [Methods] In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication—hepatic decompensation or hepatocellular carcinoma (HCC)—or requiring liver transplant after SVR. [Results] During a median (Q1–Q3) follow-up of 31.6 (22.7–36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28–9.12]), pretreatment CPT class B or C (62.5 [3.08–1246.42]) and MELD scores (1.37 [1.03–1.82]), CPT class B or C at SVR (10.71 [1.32–87.01]), CD4 cell counts, This work was supported in part by the Instituto de Salud Carlos III (Project “P16/01443”), integrated in the national I+D+i 2013–2016 and co-funded by the European Union (European Regional Development Fund/European Social Fund, “Investing in your future”), by the Spanish Network for AIDS investigation (RIS) (www.red.es/redes/inicio) (RD16/0025/0040), as a part of the Nacional I+ D+I, ISCIII Subdirección General de Evaluación and the European Fund for Development of Regions (FEDER) and by GEHEP-Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (GEHEP-011 project). JAP has received a research extension grant from the Programa de Intensificación de la Actividad de Investigación del Servicio Nacional de Salud Carlos III (3SNS).

Published
2020

39. High rate of major drug–drug interactions of lopinavir–ritonavir for COVID-19 treatment

Author

Instituto de Salud Carlos III, Macías Sánchez, Juan, Pinilla, Ana, Lao-Domínguez, Francisco A., Corma-Gómez, Anaïs, Contreras-Macías, Enrique, González-Serna, A., Gutiérrez-Pizarraya, A., Fernández-Fuertes, Marta, Morillo-Verdugo, Ramón, Trigo, Marta, Real, Luis Miguel, Pineda, Juan A., Instituto de Salud Carlos III, Macías Sánchez, Juan, Pinilla, Ana, Lao-Domínguez, Francisco A., Corma-Gómez, Anaïs, Contreras-Macías, Enrique, González-Serna, A., Gutiérrez-Pizarraya, A., Fernández-Fuertes, Marta, Morillo-Verdugo, Ramón, Trigo, Marta, Real, Luis Miguel, and Pineda, Juan A.

Abstract

The impact of drug–drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69–85%) patients, and in 33 (26%, 95% CI 19–35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10–731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04–0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.

Published
2020

40. Liver stiffness at the time of sustained virological response predicts the clinical outcome in HIV/HCV-coinfected patients with advanced fibrosis treated with direct-acting antivirals

Author

Instituto de Salud Carlos III, European Commission, Red Española de Investigación en SIDA, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, Corma-Gómez, Anaïs, Macías Sánchez, Juan, Téllez, Francisco, Freyre, Carolina, Morano-Amado, Luis E., Rivero-Juárez, Antonio, Ríos-Villegas, María José, Alados, Juan Carlos, Vera-Méndez, Francisco Jesús, Merchante, Nicolás, Palacios, Rosario, Granados, Rafael, Merino, Dolores, De Los Santos, Ignacio, Pineda, Juan A., Instituto de Salud Carlos III, European Commission, Red Española de Investigación en SIDA, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, Corma-Gómez, Anaïs, Macías Sánchez, Juan, Téllez, Francisco, Freyre, Carolina, Morano-Amado, Luis E., Rivero-Juárez, Antonio, Ríos-Villegas, María José, Alados, Juan Carlos, Vera-Méndez, Francisco Jesús, Merchante, Nicolás, Palacios, Rosario, Granados, Rafael, Merino, Dolores, De Los Santos, Ignacio, and Pineda, Juan A.

Abstract

[Background] Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). [Methods] In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication—hepatic decompensation or hepatocellular carcinoma (HCC)—or requiring liver transplant after SVR. [Results] During a median (Q1–Q3) follow-up of 31.6 (22.7–36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28–9.12]), pretreatment CPT class B or C (62.5 [3.08–1246.42]) and MELD scores (1.37 [1.03–1.82]), CPT class B or C at SVR (10.71 [1.32–87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49–13.15]), FIB-4 index at SVR (1.39 [1.13–1.70]), and LS at SVR (1.05 [1.02–1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. [Conclusions] LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.

Published
2020

42. HIV co-infection is associated with lower risk of liver cancer after HCV-cure

Author

Corma-Gómez, Anaïs, primary, Sanchez, Juan Macias, additional, Pérez, Francisco Téllez, additional, Morano Amado, Luis Enrique, additional, Rivero-Juarez, Antonio, additional, Serrano, Miriam, additional, Riós Villegas, Maria José, additional, Alados Arboledas, Juan Carlos, additional, Vera-Méndez, Francisco J, additional, Merchante, Nicolas, additional, Villalobos, Marina, additional, De Los Santos, Ignacio, additional, Geijo, Paloma, additional, Merino, Dolores, additional, Imaz, Arkaitz, additional, Galindo, Maria José, additional, and Pineda, Juan, additional

Published
2020
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43. A genome‐wide association study on low susceptibility to hepatitis C virus infection (GEHEP012 study)

Author

European Commission, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, Junta de Andalucía, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Real, Luis Miguel, Fernández‐Fuertes, Marta, Sáez, María Eugenia, Rivero-Juárez, Antonio, Frías, Mario, Téllez, Francisco, Santos, Jesús, Merino, Dolores, Moreno-Grau, Sonia, Gómez-Salgado, Juan, González-Serna, Manuel Alejandro, Corma-Gómez, Anaïs, Ruiz, Agustín, Macías Sánchez, Juan, Pineda, Juan A., European Commission, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, Junta de Andalucía, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Real, Luis Miguel, Fernández‐Fuertes, Marta, Sáez, María Eugenia, Rivero-Juárez, Antonio, Frías, Mario, Téllez, Francisco, Santos, Jesús, Merino, Dolores, Moreno-Grau, Sonia, Gómez-Salgado, Juan, González-Serna, Manuel Alejandro, Corma-Gómez, Anaïs, Ruiz, Agustín, Macías Sánchez, Juan, and Pineda, Juan A.

Abstract

[Background] A low proportion of individuals repeatedly exposed to the hepatitis C virus (HCV) remain uninfected. This condition could have a genetic basis but it is not known whether or not it is mainly driven by a high‐penetrance common allele., [Objective] To explore whether low susceptibility to HCV infection is mainly driven by a high‐penetrance common allele., [Methods] In this genome‐wide association study (GWAS), a total of 804 HCV‐seropositive individuals and 27 high‐risk HCV‐seronegative (HRSN) subjects were included. Plink and Magma software were used to carry out single nucleotide polymorphism (SNP)‐based and gene‐based association analyses respectively., [Results] No SNP nor any gene was associated with low susceptibility to HCV infection after multiple testing correction. However, SNPs previously associated with this trait and allocated within the LDLR gene, rs5925 and rs688, were also associated with this condition in our study under a dominant model (24 out of 27 [88.9%] rs5925‐C carriers in the HRSN group vs 560 of 804 [69.6%] rs5925‐C carriers in the HCV‐seropositive group, P = 0.031, odds ratio [OR] = 3.48; 95% confidence interval [CI] = 1.04‐11.58; and 24 out of 27 [88.9%] rs688‐T carriers in the HRSN group vs 556 of 804 [69.1%] rs688‐T carriers in the HCV‐seropositive group, P = 0.028, OR = 3.57, 95% CI = 1.65‐11.96)., [Conclusions] Low susceptibility to HCV infection does not seem to be mainly driven by a high‐penetrant common allele. By contrast, it seems a multifactorial trait where genes such as LDLR could be involved.

Published
2019

44. Higher relapse rate among HIV/HCV-coinfected patients receiving sofosbuvir/ledipasvir for 8 vs 12 weeks

Author

Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Red Española de Investigación en SIDA, Corma-Gómez, Anaïs, Macías Sánchez, Juan, Merino, Dolores, Téllez, Francisco, Granados, Rafael, Morano-Amado, Luis E., De Los Santos, Ignacio, Vera-Méndez, Francisco Jesús, Collado, Antonio, Palacios, Rosario, Pineda, Juan A., Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Red Española de Investigación en SIDA, Corma-Gómez, Anaïs, Macías Sánchez, Juan, Merino, Dolores, Téllez, Francisco, Granados, Rafael, Morano-Amado, Luis E., De Los Santos, Ignacio, Vera-Méndez, Francisco Jesús, Collado, Antonio, Palacios, Rosario, and Pineda, Juan A.

Abstract

[Objectives] To compare the efficacy of sofosbuvir/ledipasvir (SOF/LDV) for 8 weeks (SL8) versus a 12-week course of SOF/LDV (SL12) among HIV/HCV-coinfected patients in clinical practice. In addition we compared sustained virological response (SVR) rates achieved with SL8 in HCV-monoinfected and HIV/HCV-coinfected patients in a real life setting., [Methods] HCV-infected patients were retrospectively selected from the HEPAVIR-DAA and GEHEP-MONO real-life prospective cohorts if they fulfilled the following criteria: 1) Infected with genotype 1; 2) Treatment with SL8 or SL12; 3) Treatment naïve prior to receiving SL8 or SL12; 4) Absence of cirrhosis; 5) Baseline HCV RNA<6 × 106 IU/mL; 6) Reached the scheduled time-point for SVR (SVR12) assessment. SVR12 and relapse rates of HCV-monoinfected and HIV/HCV-coinfected patients were compared on an intention to treat basis. The responses with SL8 and SL12 were also compared., [Results] In the SL8 group, 107 (51%) HCV-monoinfected and 102 (49%) HIV/HCV-coinfected patients were included. One hundred and sixty-four (43%) HCV-monoinfected subjects and 220 (57%) HIV/HCV-coinfected patients received SL12. SVR12 rates for HIV/HCV-coinfected patients treated with SL8 vs SL12 were SVR12 92.2% vs. 97.3% (p = 0.044) and the respective relapse rates were 4.9% vs. 0.5% (p = 0.013). SVR12 rates for SL8 among HCV-monoinfected and HIV/HCV-coinfected patients were: 96.3% vs. 92.2% (p = 0.243), respectively. The corresponding relapse rates were 0.9% vs. 4.9% (p = 0.112)., [Conclusion] HIV/HCV-coinfected patients reach high rates of SVR12 with SL8, although lower than with SL12, mainly due to a higher probability of relapse. SVR12 rates with SL8 are numerically lower and the proportion of relapses higher in HIV/HCVcoinfected patients than in HCV-monoinfected subjects.

Published
2019

45. Genetic markers of lipid metabolism genes associated with low susceptibility to HCV infection

Author

Junta de Andalucía, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, Instituto de Salud Carlos III, European Commission, Ministerio de Economía, Industria y Competitividad (España), Fundación la Caixa, Grifols, Real, Luis Miguel, Macías Sánchez, Juan, Rivero-Juárez, Antonio, Téllez, Francisco, Merino, Dolores, Moreno-Grau, Sonia, Orellana, Adelina, Gómez-Salgado, Juan, Sáez, María Eugenia, Frías, Mario, Corma-Gómez, Anaïs, Merchante, Nicolás, Ruiz, Agustín, Caruz, Antonio, Pineda, Juan A., Junta de Andalucía, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, Instituto de Salud Carlos III, European Commission, Ministerio de Economía, Industria y Competitividad (España), Fundación la Caixa, Grifols, Real, Luis Miguel, Macías Sánchez, Juan, Rivero-Juárez, Antonio, Téllez, Francisco, Merino, Dolores, Moreno-Grau, Sonia, Orellana, Adelina, Gómez-Salgado, Juan, Sáez, María Eugenia, Frías, Mario, Corma-Gómez, Anaïs, Merchante, Nicolás, Ruiz, Agustín, Caruz, Antonio, and Pineda, Juan A.

Abstract

Due to the relation between lipids and Hepatitis C virus (HCV) life-cycle, we aimed to explore the existence of single nucleotide polymorphisms (SNPs) associated with low susceptibility to HCV-infection within lipid metabolism genes. This was a case-control study in three phases: (I) allelic frequencies of 9 SNPs within 6 genes were compared in 404 HCV-infected patients and 801 population controls; (II) results were validated in 602 HCV-infected individuals and 1352 controls; (III) results were confirmed in 30 HCV-exposed uninfected (EU) individuals. In phase I, only the LDLRAP1-rs4075184-A allele was differentially distributed in patients and controls (358 of 808 alleles [44.3%] and 807 of 1602 alleles [50.3%], respectively) (p = 0.004). In phase II, the A allele frequency was 547 of 1204 alleles (45.4%) in patients and 1326 of 2704 alleles (49.0%) in controls (p = 0.037). This frequency in EU was 36 of 60 alleles (60%), which was higher than that observed in patients from phase I (p = 0.018) and phase II (p = 0.027). The LDLRAP1-mRNA expression was lower in AA carriers than in non-AA carriers (median [Q1-Q3]: 0.85 [0.17–1.75] relative-units [ru] versus 1.71 [1.00–2.73] ru; p = 0.041). Our results suggest that LDLRAP1-rs4075184-A allele is associated with lower susceptibility to HCV-infection and with reduced expression of LDLRAP1-mRNA.

Published
2019

46. Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower Risk of Hepatocellular Carcinoma After Sustained Virological Response to Direct-acting Antivirals in Hepatitis C Infected Patients With Advanced Fibrosis.

Author

Corma-Gómez, Anaïs, Macías, Juan, Lacalle-Remigio, Juan Ramón, Téllez, Francisco, Morano, Luis, Rivero, Antonio, Serrano, Miriam, Ríos, María José, Vera-Méndez, Francisco Jesús, Alados, Juan Carlos, Real, Luis Miguel, Palacios, Rosario, Santos, Ignacio De Los, Imatz, Arkaitz, Pineda, Juan Antonio, and groups, RIS-HEP13 and GEHEP 011 study

Subjects
*HIV infection complications, *HIV infections, *CONFIDENCE intervals, *ANTIVIRAL agents, *CIRRHOSIS of the liver, *FISHER exact test, *MANN Whitney U Test, *RISK assessment, *T-test (Statistics), *DESCRIPTIVE statistics, *CHI-squared test, *DATA analysis software, *HEPATOCELLULAR carcinoma, *LONGITUDINAL method, *DISEASE risk factors
Abstract

Background The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA). Methods Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients. Results In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1–Q3) follow-up time of 43 (31–49) months, 19 (1.8%) patients developed HCC (11 [3.0%]; HCV-monoinfected, 8[1.2%]; HIV/HCV-coinfected individuals; P =.013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio [sHR] = 0.27, 95% confidence interval [CI]:.08–.90; P =.034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5–24.9; P <.001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01–1.86; P =.043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01–1.06, for 1 kPa increase; P =.011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI:.11–.85). Conclusions Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated. [ABSTRACT FROM AUTHOR]

Published
2021
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47. Higher relapse rate among HIV/HCV-coinfected patients receiving sofosbuvir/ledipasvir for 8 vs 12 weeks

Author

Corma-Gómez, Anaïs, primary, Macías, Juan, additional, Merino Muñoz, Dolores, additional, Téllez, Francisco, additional, Granados, Rafael, additional, Morano, Luis E., additional, De Los Santos Gil, Ignacio, additional, Vera-Méndez, Francisco J., additional, Collado, Antonio, additional, Palacios, Rosario, additional, and Pineda, Juan A., additional

Published
2019
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48. Liver Stiffness–Based Strategies Predict Absence of Variceal Bleeding in Cirrhotic Hepatitis C Virus–Infected Patients With and Without Human Immunodeficiency Virus Coinfection After Sustained Virological Response.

Author

Corma-Gómez, Anaïs, Macías, Juan, Morano, Luis, Rivero, Antonio, Téllez, Francisco, Ríos, Maria José, Santos, Marta, Serrano, Miriam, Palacios, Rosario, Merino, Dolores, Real, Luis Miguel, Santos, Ignacio De Los, Vera-Méndez, Francisco J, Galindo, Maria José, Pineda, Juan A, and Groups, RIS-HEP13 and GEHEP 011 Study

Subjects
*GASTROINTESTINAL hemorrhage, *HIV infections, *RESEARCH, *PREDICTIVE tests, *CONFIDENCE intervals, *CIRRHOSIS of the liver, *HEPATITIS C, *ESOPHAGEAL varices, *MEDICAL cooperation, *ANTIRETROVIRAL agents, *DIGESTIVE system endoscopic surgery, *RISK assessment, *LIVER diseases, *MIXED infections, *DESCRIPTIVE statistics, *LONGITUDINAL method, *DISEASE risk factors, *HEMORRHAGE risk factors
Abstract

Background In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)–based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. Methods This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral–based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. Results Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%–100%), 100% (95% CI 97.8%–100%), and 100% (95% CI 98%–100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. Conclusions After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode. [ABSTRACT FROM AUTHOR]

Published
2021
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49. Consumo de psicofármacos y exposición a toxinas bacterianas vehiculizadas por alimentos: una asociación peligrosa

Author

Corma-Gómez, Anaïs, López-Sepúlveda, Rocío, Capitán-del Río, Inés, Sánchez Mariscal, María Dolores, and López-Hernández, Begoña

Subjects
Adult, Hospitals, Psychiatric, Male, Brote, Adolescent, Clostridium perfringens, Bacterial Toxins, Disease Outbreaks, Cohort Studies, Foodborne Diseases, Young Adult, Humans, Toxiinfección alimentaria, Prospective Studies, Child, Aged, Retrospective Studies, Psychotropic Drugs, Vulnerable people, Outbreak, Antiepilépticos, Middle Aged, Food borne disease, Spain, Personas vulnerables, Anticonvulsants, Female
Abstract

RESUMEN Objetivo Describir y analizar desde el punto de vista clínico y epidemiológico un brote de toxiinfección alimentaria en una institución de enfermos psiquiátricos de Granada, en 2015, y examinar si el tratamiento con psicofármacos constituye un factor de riesgo para desarrollar una toxiinfección alimentaria, analizando los grados de susceptibilidad según el grupo terapéutico consumido. Método Estudio ambispectivo de cohortes. La unidad de análisis fueron los residentes. Se realizó búsqueda activa de casos, encuesta alimentaria y búsqueda de otros riesgos, e inspección alimentaria. Se estudiaron variables de persona, lugar y tiempo. Análisis descriptivo (frecuencias absolutas y relativas), cálculo de las tasas de ataque por pabellón y por menú. Análisis bivariado (ji al cuadrado, t de Student) y riesgo relativo como medida de la fuerza de asociación. Análisis multivariado mediante regresión logística para el análisis de riesgos de la medicación. Resultados Se contabilizaron 18 casos con diarrea sin fiebre (periodo de incubación de 6-16 horas), de carácter leve y autolimitado. Las manifestaciones clínicas, la agrupación temporal de casos y las características de los alimentos ingeridos centraron la sospecha en una toxina bacteriana. A igualdad en el resto de variables, los grupos terapéuticos N03AF y N03AG confirieron mayor riesgo de enfermar (odds ratio [OR]: 8,626; intervalo de confianza del 95% [IC95%]: 2,050-36,308; p=0,003; y OR: 14,516; IC95%: 3,155-66,784; p=0,001, respectivamente). Conclusión La disminución del tránsito intestinal causada por la administración de antiepilépticos puede aumentar el tiempo de exposición de la mucosa intestinal a la toxina, aumentando el riesgo de enfermar y de padecer complicaciones. Debe realizarse un esfuerzo higiénico suplementario en este tipo de instituciones para prevenir estas afecciones. ABSTRACT Objective To describe and analyse from a clinical and epidemiological point of view, a food borne outbreak in a psychiatric institution in Granada, in 2015, and to examine whether treatment with psychoactive drugs constitutes a risk factor for the development of a food borne disease, analysing the degree of susceptibility according to the therapeutic group consumed. Method Ambispective cohort study. Residents were the unit of analysis. Our group carried out an active case search and a food survey. A search for other risks was developed as well as a food inspection. Location, time and individual variables were studied. A descriptive analysis was conducted (absolute and relative frequencies). Calculation of attack rates by building and by menu was made. Bi-variant analysis (Chi-square test, t-Student test) and relative risk were used as a measure of strength of association. For risk analysis of medication, a multivariate analysis using logistic regression was carried out. Results 18 cases with diarrhea without fever were found (incubation period from 6 to 16hours). Cases were mild and self-limiting. The clinical manifestations, the temporal grouping of cases and the characteristics of the ingested foods, focused suspicion on a bacterial toxin. Being equal in the rest of variables, the N03AF, and N03AG therapeutic groups confer greater risk of disease (odds ratio [OR]: 8.626; 95% confidence interval [95%CI]: 2.050-36.308; p=0.003; and OR: 14.516; 95%CI: 3.155-66.784; p=0.001, respectively). Conclusion Decreased intestinal transit, caused by the administration of anticonvulsants, may increase exposure time of the intestinal mucosa to the toxin, increasing the risk of disease and suffering from complications. An additional hygienic effort should be made in this type of institution to prevent these pathologies.

Published
2017

50. MPOX VIRUS INFECTION IS MORE SEVERE IN PATIENTS WITH UNCONTROLLED HIV INFECTION.

Author

Corma-Gómez, Anaïs, Santos, Marta, Cabello, Alfonso, Morante-Ruiz, Miguel, Al-Hayani, Aws Waleed, Acosta, Irene Carrillo, García-Fraile, Lucio, Gómez-Ayerbe, Cristina, Rodrigo-Domínguez, David, Reus, Sergio, Silva Klug, Ana C., De la Rosa-riestra, Sandra, Ferrer-Ribera, Ana, Pineda, Juan A., and Macías, Juan

Published
2023

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