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274 results on '"Iruzubieta P"'

1. Clinical and imaging spectrum of non-congenital dominant ACTN2 myopathy

Author

Iruzubieta, Pablo, Verdú-Díaz, José, Töpf, Ana, Luce, Leonela, Claeys, Kristl G., De Ridder, Willem, González-Quereda, Lidia, de Fuenmayor-Fernández de la Hoz, Carlos Pablo, Poza, Juan José, Zulaica, Miren, de Jonghe, Peter, Duff, Jennifer, Mroczek, Magdalena, Martín-Jiménez, Paloma, Hernández-Laín, Aurelio, Domínguez-González, Cristina, Baets, Jonathan, Gallano, Pia, Díaz-Manera, Jordi, Straub, Volker, López de Munain, Adolfo, and Fernandez-Torron, Roberto

Published
2025
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2. Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis

Author

Zufiría, Mónica, Pikatza-Menoio, Oihane, Garciandia-Arcelus, Maddi, Bengoetxea, Xabier, Jiménez, Andrés, Elicegui, Amaia, Levchuk, María, Arnold-García, Olatz, Ondaro, Jon, Iruzubieta, Pablo, Rodríguez-Gómez, Laura, Fernández-Pelayo, Uxoa, Muñoz-Oreja, Mikel, Aiastui, Ana, García-Verdugo, José Manuel, Herranz-Pérez, Vicente, Zulaica, Miren, Poza, Juan José, Ruiz-Onandi, Rebeca, Fernández-Torrón, Roberto, Espinal, Juan Bautista, Bonilla, Mario, Lersundi, Ana, Fernández-Eulate, Gorka, Riancho, Javier, Vallejo-Illarramendi, Ainara, Holt, Ian James, Sáenz, Amets, Malfatti, Edoardo, Duguez, Stéphanie, Blázquez, Lorea, López de Munain, Adolfo, Gerenu, Gorka, Gil-Bea, Francisco, and Alonso-Martín, Sonia

Published
2024
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3. Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles

Author

Martínez‐Arranz, Ibon, Bruzzone, Chiara, Noureddin, Mazen, Gil‐Redondo, Ruben, Mincholé, Itziar, Bizkarguenaga, Maider, Arretxe, Enara, Iruarrizaga‐Lejarreta, Marta, Fernández‐Ramos, David, Lopitz‐Otsoa, Fernando, Mayo, Rebeca, Embade, Nieves, Newberry, Elizabeth, Mittendorf, Bettina, Izquierdo‐Sánchez, Laura, Smid, Vaclav, Arnold, Jorge, Iruzubieta, Paula, Castaño, Ylenia Pérez, Krawczyk, Marcin, Marigorta, Urko M, Morrison, Martine C, Kleemann, Robert, Martín‐Duce, Antonio, Hayardeny, Liat, Vitek, Libor, Bruha, Radan, de la Fuente, Rocío Aller, Crespo, Javier, Romero‐Gomez, Manuel, Banales, Jesus M, Arrese, Marco, Cusi, Kenneth, Bugianesi, Elisabetta, Klein, Samuel, Lu, Shelly C, Anstee, Quentin M, Millet, Oscar, Davidson, Nicholas O, Alonso, Cristina, and Mato, José M

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Heart Disease, Cardiovascular, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Genetics, Liver Disease, Atherosclerosis, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Animals, Apolipoproteins B, Cardiovascular Diseases, Cholesterol, VLDL, Heart Disease Risk Factors, Lipoproteins, VLDL, Liver, Mice, Non-alcoholic Fatty Liver Disease, Phospholipases, Risk Factors, Triglycerides, Clinical Sciences, Immunology, Gastroenterology & Hepatology, Clinical sciences
Abstract

Background and aimsWe previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors.Approach and resultsWe analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6 , and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A.ConclusionsMetabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.

Published
2022

5. Targeting Hepatic Glutaminase 1 Ameliorates Non-alcoholic Steatohepatitis by Restoring Very-Low-Density Lipoprotein Triglyceride Assembly

Author

Simon, Jorge, Nuñez-García, Maitane, Fernández-Tussy, Pablo, Barbier-Torres, Lucía, Fernández-Ramos, David, Gómez-Santos, Beatriz, Buqué, Xabier, Lopitz-Otsoa, Fernando, Goikoetxea-Usandizaga, Naroa, Serrano-Macia, Marina, Rodriguez-Agudo, Rubén, Bizkarguenaga, Maider, Zubiete-Franco, Imanol, Gutiérrez-de Juan, Virginia, Cabrera, Diana, Alonso, Cristina, Iruzubieta, Paula, Romero-Gomez, Manuel, van Liempd, Sebastiaan, Castro, Azucena, Nogueiras, Ruben, Varela-Rey, Marta, Falcón-Pérez, Juan Manuel, Villa, Erica, Crespo, Javier, Lu, Shelly C, Mato, Jose M, Aspichueta, Patricia, Delgado, Teresa C, and Martínez-Chantar, María Luz

Subjects
Biochemistry and Cell Biology, Biological Sciences, Hepatitis, Chronic Liver Disease and Cirrhosis, Liver Disease, Nutrition, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Adult, Animals, Choline, Disease Models, Animal, Female, Glutaminase, Hepatocytes, Humans, Lipid Metabolism, Lipoproteins, VLDL, Liver, Male, Methionine, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease, Oxidative Stress, Phospholipids, Triglycerides, GLS1, GLS2, NAFLD, NASH, TCA cycle, VLDL, folate cycle, glutaminase, methionine cycle, phospholipids, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

Non-alcoholic steatohepatitis (NASH) is characterized by the accumulation of hepatic fat in an inflammatory/fibrotic background. Herein, we show that the hepatic high-activity glutaminase 1 isoform (GLS1) is overexpressed in NASH. Importantly, GLS1 inhibition reduces lipid content in choline and/or methionine deprivation-induced steatotic mouse primary hepatocytes, in human hepatocyte cell lines, and in NASH mouse livers. We suggest that under these circumstances, defective glutamine fueling of anaplerotic mitochondrial metabolism and concomitant reduction of oxidative stress promotes a reprogramming of serine metabolism, wherein serine is shifted from the generation of the antioxidant glutathione and channeled to provide one-carbon units to regenerate the methionine cycle. The restored methionine cycle can induce phosphatidylcholine synthesis from the phosphatidylethanolamine N-methyltransferase-mediated and CDP-choline pathways as well as by base-exchange reactions between phospholipids, thereby restoring hepatic phosphatidylcholine content and very-low-density lipoprotein export. Overall, we provide evidence that hepatic GLS1 targeting is a valuable therapeutic approach in NASH.

Published
2020

6. Reperfusion therapy in acute ischaemic stroke due to cervical and cerebral artery dissection: Results from a Spanish multicentre study

Author

Campo-Caballero, D., de la Riva, P., de Arce, A., Martínez-Zabaleta, M., Rodríguez-Antigüedad, J., Ekiza, J., Iruzubieta, P., Purroy, F., Fuentes, B., de Lera Alfonso, M., Krupinski, J., Mengual Chirife, J.J., Palomeras, E., Guisado-Alonso, D., Rodríguez-Yáñez, M., Ustrell, X., Tejada García, J., de Felipe Mimbrera, A., Paré-Curell, M., Tembl, J., Cajaraville, S., Garcés, M., and Serena, J.

Published
2023
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7. Tratamiento de reperfusión en el ictus isquémico agudo por disección arterial cervicocerebral: descripción de los resultados de un estudio nacional multicéntrico

Author

Campo-Caballero, D., de la Riva, P., de Arce, A., Martínez-Zabaleta, M., Rodríguez-Antigüedad, J., Ekiza, J., Iruzubieta, P., Purroy, F., Fuentes, B., de Lera Alfonso, M., Krupinski, J., Mengual Chirife, J.J., Palomeras, E., Guisado-Alonso, D., Rodríguez-Yáñez, M., Ustrell, X., Tejada García, J., de Felipe Mimbrera, A., Paré-Curell, M., Tembl, J., Cajaraville, S., Garcés, M., and Serena, J.

Published
2023
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8. miR-873-5p targets mitochondrial GNMT-Complex II interface contributing to non-alcoholic fatty liver disease

Author

Fernández-Tussy, Pablo, Fernández-Ramos, David, Lopitz-Otsoa, Fernando, Simón, Jorge, Barbier-Torres, Lucía, Gomez-Santos, Beatriz, Nuñez-Garcia, Maitane, Azkargorta, Mikel, Juan, Virginia Gutiérrez-de, Serrano-Macia, Marina, Rodríguez-Agudo, Rubén, Iruzubieta, Paula, Anguita, Juan, Castro, Rui E, Champagne, Devin, Rincón, Mercedes, Elortza, Felix, Arslanow, Anita, Krawczyk, Marcin, Lammert, Frank, Kirchmeyer, Mélanie, Behrmann, Iris, Crespo, Javier, Lu, Shelly C, Mato, José M, Varela-Rey, Marta, Aspichueta, Patricia, Delgado, Teresa C, and Martínez-Chantar, María L

Subjects
Liver Disease, Biotechnology, Hepatitis, Digestive Diseases, Complementary and Integrative Health, Chronic Liver Disease and Cirrhosis, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Metabolic and endocrine, Good Health and Well Being, Adult, Animals, Antagomirs, Disease Models, Animal, Electron Transport Complex II, Female, Glycine N-Methyltransferase, Hepatocytes, Humans, Lipid Peroxidation, Liver, Male, Mice, Mice, Inbred C57BL, MicroRNAs, Middle Aged, Mitochondria, Non-alcoholic Fatty Liver Disease, Up-Regulation, NASH, GNMT, beta-oxidation, Metabolism, microRNA, β-oxidation, Biochemistry and Cell Biology, Physiology
Abstract

OBJECTIVE:Non-alcoholic fatty liver disease (NAFLD) is a complex pathology in which several dysfunctions, including alterations in metabolic pathways, mitochondrial functionality and unbalanced lipid import/export, lead to lipid accumulation and progression to inflammation and fibrosis. The enzyme glycine N-methyltransferase (GNMT), the most important enzyme implicated in S-adenosylmethionine catabolism in the liver, is downregulated during NAFLD progression. We have studied the mechanism involved in GNMT downregulation by its repressor microRNA miR-873-5p and the metabolic pathways affected in NAFLD as well as the benefit of recovery GNMT expression. METHODS:miR-873-5p and GNMT expression were evaluated in liver biopsies of NAFLD/NASH patients. Different in vitro and in vivo NAFLD murine models were used to assess miR-873-5p/GNMT involvement in fatty liver progression through targeting of the miR-873-5p as NAFLD therapy. RESULTS:We describe a new function of GNMT as an essential regulator of Complex II activity in the electron transport chain in the mitochondria. In NAFLD, GNMT expression is controlled by miR-873-5p in the hepatocytes, leading to disruptions in mitochondrial functionality in a preclinical murine non-alcoholic steatohepatitis (NASH) model. Upregulation of miR-873-5p is shown in the liver of NAFLD/NASH patients, correlating with hepatic GNMT depletion. Importantly, NASH therapies based on anti-miR-873-5p resolve lipid accumulation, inflammation and fibrosis by enhancing fatty acid β-oxidation in the mitochondria. Therefore, miR-873-5p inhibitor emerges as a potential tool for NASH treatment. CONCLUSION:GNMT participates in the regulation of metabolic pathways and mitochondrial functionality through the regulation of Complex II activity in the electron transport chain. In NAFLD, GNMT is repressed by miR-873-5p and its targeting arises as a valuable therapeutic option for treatment.

Published
2019

10. Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients

Author

Serrano-Maciá, Marina, Lachiondo-Ortega, Sofia, Iruzubieta, Paula, Goikoetxea-Usandizaga, Naroa, Bosch, Alexandre, Egia-Mendikute, Leire, Jiménez-Lasheras, Borja, Azkargorta, Mikel, Elortza, Félix, Martinez-Redondo, Diana, Castro, Begoña, Lozano, Juan J., Nogueiras, Ruben, Irure-Ventura, Juan, Crespo, Javier, Palazón, Asís, Fariñas, María Carmen, Delgado, Teresa C., López-Hoyos, Marcos, and Martínez-Chantar, Maria L.

Published
2022
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11. Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage

Author

González-Recio, Irene, Simón, Jorge, Goikoetxea-Usandizaga, Naroa, Serrano-Maciá, Marina, Mercado-Gómez, Maria, Rodríguez-Agudo, Rubén, Lachiondo-Ortega, Sofía, Gil-Pitarch, Clàudia, Fernández-Rodríguez, Carmen, Castellana, Donatello, Latasa, Maria U., Abecia, Leticia, Anguita, Juan, Delgado, Teresa C., Iruzubieta, Paula, Crespo, Javier, Hardy, Serge, Petrov, Petar D., Jover, Ramiro, Avila, Matías A., Martín, César, Schaeper, Ute, Tremblay, Michel L., Dear, James W., Masson, Steven, McCain, Misti Vanette, Reeves, Helen L., Andrade, Raul J., Lucena, M. Isabel, Buccella, Daniela, Martínez-Cruz, Luis Alfonso, and Martínez-Chantar, Maria L

Published
2022
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12. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

Author

Andrade, R.J., Lucena, M.I., Stephens, C., Cortés, M. García, Robles-Díaz, M., Ortega-Alonso, A., Pinazo, J., Muñoz, B. García, Alcántara, R., Hernández, A., Escaño, M.D. García, del Campo, E., Medina-Cáliz, I., Sanabria-Cabrera, J., González-Jiménez, A., Sanjuán-Jiménez, R., Cueto, A., Álvarez-Álvarez, I., Bonilla, E., Di Zeo, D., Niu, H., Villanueva, M., Papineau, A., Pérez, M. Jiménez, Grande, R. González, Ortega, S. López, Santaella, I., Ocaña, A., Palomino, P., Fernández, M.C., Peláez, G., Porcel, A., Casado, M., Sánchez, M. González, Romero-Gómez, M., Millán-Domínguez, R., Fombuena, B., Gallego, R., Ampuero, J., Campo, J.A. del, Calle-Sanz, R., Rojas, L., Rojas, A., Gómez, A. Gil, Vilar, E., Soriano, G., Guarner, C., Román, E.M., Manuitt, M.A. Quijada, Arbos, R.M. Antonijoan, Delgado, J. Sánchez, Gómez, M. Vergara, Hallal, H., Oltra, E. García, Arcos, J.C. Titos, Martínez, A. Pérez, Cobarro, C. Sánchez, Caparrós, J.M. Egea, Castiella, A., Zapata, E., Arenas, J., García, A. Gómez, Esandi, F.J., Blanco, S., Odriozola, P. Martínez, Crespo, J., Iruzubieta, P., Cabezas, J., Gallego, A. Giráldez, Rodríguez Seguel, E. del P., Cuaresma, M., Gallego, J. González, Jorquera, F., Campos, S. Sánchez, Otazua, P., de Juan Gómez, A., Salmerón, J., Gila, A., Quiles, R., González, J.M., Lorenzo, S., Prieto, M., Amiel, I. Conde, Berenguer, M., García-Eliz, M., Primo, J., Molés, J.R., Garayoa, A., Carrascosa, M., Domínguez, E. Gómez, Cuevas, L., Farré, M., Montané, E., Barriocanal, A.M., Arellano, A.L., Sanz, Y., Morillas, R.M., Sala, M., Ridaura, H. Masnou, Bruguera, M., Gines, P., Lens, S., García, J.C., Mariño, Z., Guerra, M. Hernández, Sanfiel, J.M. Moreno, Fernández del Campo, C. Boada, Tejedor, M., Ferrer, R. González, Fernández, C., Gil, M. Fernández, Montero, J.L., Mata, M. de la, Olmo, J. Fuentes, Bonilla, E.M. Fernández, Moreno, J.M., Martínez-Rodenas, P., Garrido, M., Oliva, C., Rendón, P., Samaniego, J. García, Madejón, A., Calleja, J.L., Porras, J.L. Martínez, Cabriada, J.L., Pérez-Moreno, J.M., Lara, C., Stephens, Camilla, Robles-Diaz, Mercedes, Medina-Caliz, Inmaculada, Garcia-Cortes, Miren, Ortega-Alonso, Aida, Sanabria-Cabrera, Judith, Gonzalez-Jimenez, Andres, Alvarez-Alvarez, Ismael, Slim, Mahmoud, Jimenez-Perez, Miguel, Gonzalez-Grande, Rocio, Fernández, M. Carmen, Casado, Marta, Soriano, German, Román, Eva, Hallal, Hacibe, Romero-Gomez, Manuel, Castiella, Agustin, Conde, Isabel, Prieto, Martin, Moreno-Planas, Jose Maria, Giraldez, Alvaro, Moreno-Sanfiel, J. Miguel, Kaplowitz, Neil, Lucena, M. Isabel, and Andrade, Raúl J.

Published
2021
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13. The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury.

Author

Barbier-Torres, Lucía, Iruzubieta, Paula, Fernández-Ramos, David, Delgado, Teresa C, Taibo, Daniel, Guitiérrez-de-Juan, Virginia, Varela-Rey, Marta, Azkargorta, Mikel, Navasa, Nicolas, Fernández-Tussy, Pablo, Zubiete-Franco, Imanol, Simon, Jorge, Lopitz-Otsoa, Fernando, Lachiondo-Ortega, Sofia, Crespo, Javier, Masson, Steven, McCain, Misti Vanette, Villa, Erica, Reeves, Helen, Elortza, Felix, Lucena, Maria Isabel, Hernández-Alvarez, Maria Isabel, Zorzano, Antonio, Andrade, Raúl J, Lu, Shelly C, Mato, José M, Anguita, Juan, Rincón, Mercedes, and Martínez-Chantar, María Luz

Subjects
Liver, Mitochondria, Liver, Hepatocytes, Animals, Mice, Inbred C57BL, Humans, Mice, Disease Models, Animal, Acetaminophen, Rotenone, Electron Transport Complex I, Mitochondrial Proteins, Molecular Chaperones, RNA, Small Interfering, Uncoupling Agents, Adolescent, Adult, Middle Aged, Female, Male, HSP40 Heat-Shock Proteins, Gene Knockout Techniques, Young Adult, Primary Cell Culture, Drug Overdose, Chemical and Drug Induced Liver Injury, Mitochondria, Inbred C57BL, Disease Models, Animal, RNA, Small Interfering
Abstract

Acetaminophen (APAP) is the active component of many medications used to treat pain and fever worldwide. Its overuse provokes liver injury and it is the second most common cause of liver failure. Mitochondrial dysfunction contributes to APAP-induced liver injury but the mechanism by which APAP causes hepatocyte toxicity is not completely understood. Therefore, we lack efficient therapeutic strategies to treat this pathology. Here we show that APAP interferes with the formation of mitochondrial respiratory supercomplexes via the mitochondrial negative regulator MCJ, and leads to decreased production of ATP and increased generation of ROS. In vivo treatment with an inhibitor of MCJ expression protects liver from acetaminophen-induced liver injury at a time when N-acetylcysteine, the standard therapy, has no efficacy. We also show elevated levels of MCJ in the liver of patients with acetaminophen overdose. We suggest that MCJ may represent a therapeutic target to prevent and rescue liver injury caused by acetaminophen.

Published
2017

16. Deregulated neddylation in liver fibrosis

Author

Zubiete‐Franco, Imanol, Fernández‐Tussy, Pablo, Barbier‐Torres, Lucía, Simon, Jorge, Fernández‐Ramos, David, Lopitz‐Otsoa, Fernando, Juan, Virginia Gutiérrez‐de, de Davalillo, Sergio López, Duce, Antonio Martín, Iruzubieta, Paula, Taibo, Daniel, Crespo, Javier, Caballeria, Juan, Villa, Erica, Aurrekoetxea, Igor, Aspichueta, Patricia, Varela‐Rey, Marta, Lu, Shelly C, Mato, José M, Beraza, Naiara, Delgado, Teresa C, and Martínez‐Chantar, María L

Subjects
Digestive Diseases, Chronic Liver Disease and Cirrhosis, Liver Disease, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Aetiology, Oral and gastrointestinal, Good Health and Well Being, Aging, Analysis of Variance, Animals, Apoptosis, Biopsy, Needle, Cell Proliferation, Cell Survival, Cells, Cultured, Chemokine CCL4, Chemokines, Cyclopentanes, Disease Models, Animal, Hepatic Stellate Cells, Humans, Immunohistochemistry, Liver Cirrhosis, Male, Mice, Mice, Inbred C57BL, NEDD8 Protein, Pyrimidines, Random Allocation, Signal Transduction, Ubiquitins, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Abstract

Hepatic fibrosis is a global health problem currently without effective therapeutic approaches. Even though the ubiquitin-like posttranslational modification of neddylation, that conjugates Nedd8 (neural precursor cell expressed developmentally downregulated) to specific targets, is aberrant in many pathologies, its relevance in liver fibrosis (LF) remained unexplored. Our results show deregulated neddylation in clinical fibrosis and both in mouse bileductligation- and CCl4 -induced fibrosis. Importantly, neddylation inhibition, by using the pharmacological inhibitor, MLN4924, reduced liver injury, apoptosis, inflammation, and fibrosis by targeting different hepatic cell types. On one hand, increased neddylation was associated with augmented caspase 3 activity in bile-acid-induced apoptosis in mouse hepatocytes whereas neddylation inhibition ameliorated apoptosis through reduction of expression of the Cxcl1 and Ccl2 chemokines. On the other hand, chemokine receptors and cytokines, usually induced in activated macrophages, were reduced after neddylation inhibition in mouse Kupffer cells. Under these circumstances, decreased hepatocyte cell death and inflammation after neddylation inhibition could partly account for reduction of hepatic stellate cell (HSC) activation. We provide evidence that augmented neddylation characterizes activated HSCs, suggesting that neddylation inhibition could be important for resolving LF by directly targeting these fibrogenic cells. Indeed, neddylation inhibition in activated HSCs induces apoptosis in a process partly mediated by accumulation of c-Jun, whose cullin-mediated degradation is impaired under these circumstances.ConclusionNeddylation inhibition reduces fibrosis, suggesting neddylation as a potential and attractive therapeutic target in liver fibrosis. (Hepatology 2017;65:694-709).

Published
2017

17. A morphological method for ammonia detection in liver.

Author

Gutiérrez-de-Juan, Virginia, López de Davalillo, Sergio, Fernández-Ramos, David, Barbier-Torres, Lucía, Zubiete-Franco, Imanol, Fernández-Tussy, Pablo, Simon, Jorge, Lopitz-Otsoa, Fernando, de Las Heras, Javier, Iruzubieta, Paula, Arias-Loste, María Teresa, Villa, Erica, Crespo, Javier, Andrade, Raúl, Lucena, M Isabel, Varela-Rey, Marta, Lu, Shelly C, Mato, José M, Delgado, Teresa Cardoso, and Martínez-Chantar, María-Luz

Subjects
Liver, Animals, Humans, Mice, Iodides, Ammonia, Mercury Compounds, Cytological Techniques, Adolescent, Adult, Aged, Middle Aged, Child, Preschool, Male, Young Adult, Non-alcoholic Fatty Liver Disease, Child, Preschool, General Science & Technology
Abstract

Hyperammonemia is a metabolic condition characterized by elevated levels of ammonia and a common event in acute liver injury/failure and chronic liver disease. Even though hepatic ammonia levels are potential predictive factors of patient outcome, easy and inexpensive methods aiming at the detection of liver ammonia accumulation in the clinical setting remain unavailable. Thus, herein we have developed a morphological method, based on the utilization of Nessler´s reagent, to accurately and precisely detect the accumulation of ammonia in biological tissue. We have validated our method against a commercially available kit in mouse tissue samples and, by using this modified method, we have confirmed the hepatic accumulation of ammonia in clinical and animal models of acute and chronic advanced liver injury as well as in the progression of fatty liver disease. Overall, we propose a morphological method for ammonia detection in liver that correlates well with the degree of liver disease severity and therefore can be potentially used to predict patient outcome.

Published
2017

18. Esteatosis hepática metabólica

Author

Iruzubieta, P., primary, Arias-Loste, M.T., additional, del Barrio, M., additional, Echavarría, V., additional, Alonso-Peña, M., additional, and Crespo, J., additional

Published
2024
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22. Efficacy and safety of endoscopic sleeve gastroplasty versus laparoscopic sleeve gastrectomy in obese subjects with Non-Alcoholic SteatoHepatitis (NASH): study protocol for a randomized controlled trial (TESLA-NASH study)

Author

Lavín-Alconero, Lucía, Fernández-Lanas, Tatiana, Iruzubieta-Coz, Paula, Arias-Loste, Maria Teresa, Rodriguez-Duque, Juan Carlos, Rivas, Coral, Cagigal, Maria Luisa, Montalbán, Coral, Useros, Antonio Lopez, Álvarez-Cancelo, Ana, García-Saiz, Mar, and Crespo-García, Javier

Published
2021
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24. One‐step non‐invasive diagnosis of metabolic dysfunction‐associated steatohepatitis and fibrosis in high‐risk population

Author

Iruzubieta, Paula, Mayo, Rebeca, Mincholé, Itziar, Martínez‐Arranz, Ibon, Arias‐Loste, María Teresa, Ibañez‐Samaniego, Luis, Ampuero, Javier, Abad, Javier, Martín‐Mateos, Rosa, Fernández‐Laso, Ana Belén, Albillos, Agustín, Bañares, Rafael, Calleja, José Luis, Romero‐Gómez, Manuel, Aller, Rocío, and Crespo, Javier

Abstract

Type 2 Diabetes mellitus (T2DM), age, and obesity are risk factors for metabolic dysfunction‐associated steatotic liver disease (MASLD). We aimed to assess the performance of non‐invasive tests (NITs) for the diagnosis of metabolic dysfunction‐associated steatohepatitis (MASH) and fibrosis in high‐risk subjects. Multicentre cross‐sectional study that included 124 biopsy‐proven MASLD in more than 50 years‐old patients with overweight/obesity and T2DM. Vibration‐controlled transient elastography, Fibrosis‐4 index (FIB‐4), Non‐alcoholic fatty liver disease fibrosis score (NFS), OWLiver Panel (OWLiver DM2 + Metabolomics‐Advanced Steatohepatitis Fibrosis Score ‐MASEF) and FibroScan‐AST were performed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC) were calculated. NITs were assessed individually and in sequential/parallel combinations. 35 (28.2%) patients had early MASH and 66 (53.2%) had MASH with significant fibrosis (at‐risk MASH). The OWLiver Panel correctly classified 86.1% as MASH, showing an accuracy, sensitivity, specificity, PPV, and NPV of 0.77, 0.86, 0.35, 0.85, and 0.36, respectively. Class III obesity, diabetes control, or gender did not impact on the performance of the OWLiver Panel (p> 0.1). NITs for at‐risk MASH showed an AUC > 0.70 except for NFS. MASEF showed the highest accuracy and NPV for at‐risk MASH (AUC 0.77 [0.68–0.85], NPV 72%) and advanced fibrosis (AUC 0.80 [0.71–0.88], NPV 92%). Combinations of NITs for the identification of at‐risk MASH did not provide any additional benefit over using MASEF alone. One‐step screening strategy with the OWLiver Panel has high accuracy to detect MASH and at‐risk MASH in high‐risk subjects for MASLD.

Published
2024
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25. A global research priority agenda to advance public health responses to fatty liver disease

Author

Lazarus, J, Mark, H, Allen, A, Arab, J, Carrieri, P, Noureddin, M, Alazawi, W, Alkhouri, N, Alqahtani, S, Arrese, M, Bataller, R, Berg, T, Brennan, P, Burra, P, Castro-Narro, G, Cortez-Pinto, H, Cusi, K, Dedes, N, Duseja, A, Francque, S, Hagstrom, H, Huang, T, Wajcman, D, Kautz, A, Kopka, C, Krag, A, Miller, V, Newsome, P, Rinella, M, Romero, D, Sarin, S, Silva, M, Spearman, C, Tsochatzis, E, Valenti, L, Villota-Rivas, M, Zelber-Sagi, S, Schattenberg, J, Wong, V, Younossi, Z, Aberg, F, Adams, L, Al-Naamani, K, Albadawy, R, Alexa, Z, Allison, M, Alnaser, F, Alswat, K, Alvares-da-Silva, M, Alvaro, D, Alves-Bezerra, M, Andrade, R, Anstee, Q, Awuku, Y, Baatarkhuu, O, Baffy, G, Bakieva, S, Bansal, M, Barouki, R, Batterham, R, Behling, C, Belfort-DeAguiar, R, Berzigotti, A, Betel, M, Bianco, C, Bosi, E, Boursier, J, Brunt, E, Bugianesi, E, Byrne, C, Cabrera Cabrejos, M, Caldwell, S, Carr, R, Castellanos Fernandez, M, Castera, L, Castillo-Lopez, M, Caussy, C, Cerda-Reyes, E, Ceriello, A, Chan, W, Chang, Y, Charatcharoenwitthaya, P, Chavez-Tapia, N, Chung, R, Colombo, M, Coppell, K, Cotrim, H, Craxi, A, Crespo, J, Dassanayake, A, Davidson, N, De Knegt, R, de Ledinghen, V, Demir, M, Desalegn, H, Diago, M, Dillon, J, Dimmig, B, Dirac, M, Dirchwolf, M, Dufour, J, Dvorak, K, Ekstedt, M, El-Kassas, M, Elsanousi, O, Elsharkawy, A, Elwakil, R, Eskridge, W, Eslam, M, Esmat, G, Fan, J, Ferraz, M, Flisiak, R, Fortin, D, Fouad, Y, Freidman, S, Fuchs, M, Gadano, A, Gastaldelli, A, Geerts, A, Geier, A, George, J, Gerber, L, Ghazinyan, H, Gheorghe, L, Kile, D, Girala, M, Boon Bee, G, Goossens, N, Graupera, I, Gronbaek, H, Hamid, S, Hebditch, V, Henry, Z, Hickman, I, Hobbs, L, Hocking, S, Hofmann, W, Idilman, R, Iruzubieta, P, Isaacs, S, Isakov, V, Ismail, M, Jamal, M, Jarvis, H, Jepsen, P, Jornayvaz, F, Sudhamshu, K, Kakizaki, S, Karpen, S, Kawaguchi, T, Keating, S, Khader, Y, Kim, S, Kim, W, Kleiner, D, Koek, G, Joseph Komas, N, Kondili, L, Koot, B, Korenjak, M, Kotsiliti, E, Koulla, Y, Kugelmas, C, Kugelmas, M, Labidi, A, Lange, N, Lavine, J, Lazo, M, Leite, N, Lin, H, Lkhagvaa, U, Long, M, Lopez-Jaramillo, P, Lozano, A, Macedo, M, Malekzadeh, R, Marchesini, G, Marciano, S, Martinez, K, Martinez Vazquez, S, Mateva, L, Mato, J, Nlombi, C, Mccary, A, Mcintyre, J, Mckee, M, Mendive, J, Mikolasevic, I, Miller, P, Milovanovic, T, Milton, T, Moreno-Alcantar, R, Morgan, T, Motala, A, Muris, J, Musso, C, Nava-Gonzalez, E, Negro, F, Nersesov, A, Neuschwander-Tetri, B, Nikolova, D, Norris, S, Novak, K, Ocama, P, Ong, J, Ong-Go, A, Onyekwere, C, Padilla, M, Pais, R, Pan, C, Panduro, A, Panigrahi, M, Papatheodoridis, G, Paruk, I, Patel, K, Goncalves, C, Figueroa, M, Perez-Escobar, J, Pericas, J, Perseghin, G, Pessoa, M, Petta, S, Marques Souza de Oliveira, C, Prabhakaran, D, Pyrsopoulous, N, Rabiee, A, Ramji, A, Ratziu, V, Ravendhran, N, Ray, K, Roden, M, Romeo, S, Romero-Gomez, M, Rotman, Y, Rouabhia, S, Rowe, I, Sadirova, S, Alkhatry, M, Salupere, R, Satapathy, S, Schwimmer, J, Sebastiani, G, Seim, L, Seki, Y, Serme, A, Shapiro, D, Sharvadze, L, Shaw, J, Shawa, I, Shenoy, T, Shibolet, O, Shimakawa, Y, Shubrook, J, Singh, S, Sinkala, E, Skladany, L, Skrypnyk, I, Song, M, Sookoian, S, Sridharan, K, Stefan, N, Stine, J, Stratakis, N, Sheriff, D, Sundaram, S, Svegliati-Baroni, G, Swain, M, Tacke, F, Taheri, S, Tan, S, Tapper, E, Targher, G, Tcaciuc, E, Thiele, M, Tiniakos, D, Tolmane, I, Torre, A, Torres, E, Treeprasertsuk, S, Trenell, M, Turcan, S, Turcanu, A, Valantinas, J, van Kleef, L, Velarde Ruiz Velasco, J, Vesterhus, M, Vilar-Gomez, E, Waked, I, Wattacheril, J, Wedemeyer, H, Wilkins, F, Willemse, J, Wong, R, Yilmaz, Y, Yki-Jarvinen, H, Yu, M, Yumuk, V, Zeybel, M, Zheng, K, Zheng, M, Lazarus J. V., Mark H. E., Allen A. M., Arab J. P., Carrieri P., Noureddin M., Alazawi W., Alkhouri N., Alqahtani S. A., Arrese M., Bataller R., Berg T., Brennan P. N., Burra P., Castro-Narro G. E., Cortez-Pinto H., Cusi K., Dedes N., Duseja A., Francque S. M., Hagstrom H., Huang T. T. -K., Wajcman D. I., Kautz A., Kopka C. J., Krag A., Miller V., Newsome P. N., Rinella M. E., Romero D., Sarin S. K., Silva M., Spearman C. W., Tsochatzis E. A., Valenti L., Villota-Rivas M., Zelber-Sagi S., Schattenberg J. M., Wong V. W. -S., Younossi Z. M., Aberg F., Adams L., Al-Naamani K., Albadawy R. M., Alexa Z., Allison M., Alnaser F. A., Alswat K., Alvares-da-Silva M. R., Alvaro D., Alves-Bezerra M., Andrade R. J., Anstee Q. M., Awuku Y. A., Baatarkhuu O., Baffy G., Bakieva S., Bansal M. B., Barouki R., Batterham R. L., Behling C., Belfort-DeAguiar R., Berzigotti A., Betel M., Bianco C., Bosi E., Boursier J., Brunt E. M., Bugianesi E., Byrne C. J., Cabrera Cabrejos M. C., Caldwell S., Carr R., Castellanos Fernandez M. I., Castera L., Castillo-Lopez M. G., Caussy C., Cerda-Reyes E., Ceriello A., Chan W. -K., Chang Y., Charatcharoenwitthaya P., Chavez-Tapia N., Chung R. T., Colombo M., Coppell K., Cotrim H. P., Craxi A., Crespo J., Dassanayake A., Davidson N. O., De Knegt R., de Ledinghen V., Demir M., Desalegn H., Diago M., Dillon J. F., Dimmig B., Dirac M. A., Dirchwolf M., Dufour J. -F., Dvorak K., Ekstedt M., El-Kassas M., Elsanousi O. M., Elsharkawy A. M., Elwakil R., Eskridge W., Eslam M., Esmat G., Fan J. -G., Ferraz M. L., Flisiak R., Fortin D., Fouad Y., Freidman S. L., Fuchs M., Gadano A., Gastaldelli A., Geerts A., Geier A., George J., Gerber L. H., Ghazinyan H., Gheorghe L., Kile D. G., Girala M., Boon Bee G. G., Goossens N., Graupera I., Gronbaek H., Hamid S., Hebditch V., Henry Z., Hickman I. J., Hobbs L. A., Hocking S. L., Hofmann W. P., Idilman R., Iruzubieta P., Isaacs S., Isakov V. A., Ismail M. H., Jamal M. H., Jarvis H., Jepsen P., Jornayvaz F., Sudhamshu K. C., Kakizaki S., Karpen S., Kawaguchi T., Keating S. E., Khader Y., Kim S. U., Kim W., Kleiner D. E., Koek G., Joseph Komas N. P., Kondili L. A., Koot B. G., Korenjak M., Kotsiliti E., Koulla Y., Kugelmas C., Kugelmas M., Labidi A., Lange N. F., Lavine J. E., Lazo M., Leite N., Lin H. -C., Lkhagvaa U., Long M. T., Lopez-Jaramillo P., Lozano A., Macedo M. P., Malekzadeh R., Marchesini G., Marciano S., Martinez K., Martinez Vazquez S. E., Mateva L., Mato J. M., Nlombi C. M., McCary A. G., McIntyre J., McKee M., Mendive J. M., Mikolasevic I., Miller P. S., Milovanovic T., Milton T., Moreno-Alcantar R., Morgan T. R., Motala A., Muris J., Musso C., Nava-Gonzalez E. J., Negro F., Nersesov A. V., Neuschwander-Tetri B. A., Nikolova D., Norris S., Novak K., Ocama P., Ong J. P., Ong-Go A., Onyekwere C., Padilla M., Pais R., Pan C., Panduro A., Panigrahi M. K., Papatheodoridis G., Paruk I., Patel K., Goncalves C. P., Figueroa M. P., Perez-Escobar J., Pericas J. M., Perseghin G., Pessoa M. G., Petta S., Marques Souza de Oliveira C. P., Prabhakaran D., Pyrsopoulous N., Rabiee A., Ramji A., Ratziu V., Ravendhran N., Ray K., Roden M., Romeo S., Romero-Gomez M., Rotman Y., Rouabhia S., Rowe I. A., Sadirova S., Alkhatry M. S., Salupere R., Satapathy S. K., Schwimmer J. B., Sebastiani G., Seim L., Seki Y., Serme A. K., Shapiro D., Sharvadze L., Shaw J. E., Shawa I. T., Shenoy T., Shibolet O., Shimakawa Y., Shubrook J. H., Singh S. P., Sinkala E., Skladany L., Skrypnyk I., Song M. J., Sookoian S., Sridharan K., Stefan N., Stine J. G., Stratakis N., Sheriff D. S., Sundaram S. S., Svegliati-Baroni G., Swain M. G., Tacke F., Taheri S., Tan S. -S., Tapper E. B., Targher G., Tcaciuc E., Thiele M., Tiniakos D., Tolmane I., Torre A., Torres E. A., Treeprasertsuk S., Trenell M., Turcan S., Turcanu A., Valantinas J., van Kleef L. A., Velarde Ruiz Velasco J. A., Vesterhus M., Vilar-Gomez E., Waked I., Wattacheril J., Wedemeyer H., Wilkins F., Willemse J., Wong R. J., Yilmaz Y., Yki-Jarvinen H., Yu M. -L., Yumuk V., Zeybel M., Zheng K. I., Zheng M. -H., Lazarus, J, Mark, H, Allen, A, Arab, J, Carrieri, P, Noureddin, M, Alazawi, W, Alkhouri, N, Alqahtani, S, Arrese, M, Bataller, R, Berg, T, Brennan, P, Burra, P, Castro-Narro, G, Cortez-Pinto, H, Cusi, K, Dedes, N, Duseja, A, Francque, S, Hagstrom, H, Huang, T, Wajcman, D, Kautz, A, Kopka, C, Krag, A, Miller, V, Newsome, P, Rinella, M, Romero, D, Sarin, S, Silva, M, Spearman, C, Tsochatzis, E, Valenti, L, Villota-Rivas, M, Zelber-Sagi, S, Schattenberg, J, Wong, V, Younossi, Z, Aberg, F, Adams, L, Al-Naamani, K, Albadawy, R, Alexa, Z, Allison, M, Alnaser, F, Alswat, K, Alvares-da-Silva, M, Alvaro, D, Alves-Bezerra, M, Andrade, R, Anstee, Q, Awuku, Y, Baatarkhuu, O, Baffy, G, Bakieva, S, Bansal, M, Barouki, R, Batterham, R, Behling, C, Belfort-DeAguiar, R, Berzigotti, A, Betel, M, Bianco, C, Bosi, E, Boursier, J, Brunt, E, Bugianesi, E, Byrne, C, Cabrera Cabrejos, M, Caldwell, S, Carr, R, Castellanos Fernandez, M, Castera, L, Castillo-Lopez, M, Caussy, C, Cerda-Reyes, E, Ceriello, A, Chan, W, Chang, Y, Charatcharoenwitthaya, P, Chavez-Tapia, N, Chung, R, Colombo, M, Coppell, K, Cotrim, H, Craxi, A, Crespo, J, Dassanayake, A, Davidson, N, De Knegt, R, de Ledinghen, V, Demir, M, Desalegn, H, Diago, M, Dillon, J, Dimmig, B, Dirac, M, Dirchwolf, M, Dufour, J, Dvorak, K, Ekstedt, M, El-Kassas, M, Elsanousi, O, Elsharkawy, A, Elwakil, R, Eskridge, W, Eslam, M, Esmat, G, Fan, J, Ferraz, M, Flisiak, R, Fortin, D, Fouad, Y, Freidman, S, Fuchs, M, Gadano, A, Gastaldelli, A, Geerts, A, Geier, A, George, J, Gerber, L, Ghazinyan, H, Gheorghe, L, Kile, D, Girala, M, Boon Bee, G, Goossens, N, Graupera, I, Gronbaek, H, Hamid, S, Hebditch, V, Henry, Z, Hickman, I, Hobbs, L, Hocking, S, Hofmann, W, Idilman, R, Iruzubieta, P, Isaacs, S, Isakov, V, Ismail, M, Jamal, M, Jarvis, H, Jepsen, P, Jornayvaz, F, Sudhamshu, K, Kakizaki, S, Karpen, S, Kawaguchi, T, Keating, S, Khader, Y, Kim, S, Kim, W, Kleiner, D, Koek, G, Joseph Komas, N, Kondili, L, Koot, B, Korenjak, M, Kotsiliti, E, Koulla, Y, Kugelmas, C, Kugelmas, M, Labidi, A, Lange, N, Lavine, J, Lazo, M, Leite, N, Lin, H, Lkhagvaa, U, Long, M, Lopez-Jaramillo, P, Lozano, A, Macedo, M, Malekzadeh, R, Marchesini, G, Marciano, S, Martinez, K, Martinez Vazquez, S, Mateva, L, Mato, J, Nlombi, C, Mccary, A, Mcintyre, J, Mckee, M, Mendive, J, Mikolasevic, I, Miller, P, Milovanovic, T, Milton, T, Moreno-Alcantar, R, Morgan, T, Motala, A, Muris, J, Musso, C, Nava-Gonzalez, E, Negro, F, Nersesov, A, Neuschwander-Tetri, B, Nikolova, D, Norris, S, Novak, K, Ocama, P, Ong, J, Ong-Go, A, Onyekwere, C, Padilla, M, Pais, R, Pan, C, Panduro, A, Panigrahi, M, Papatheodoridis, G, Paruk, I, Patel, K, Goncalves, C, Figueroa, M, Perez-Escobar, J, Pericas, J, Perseghin, G, Pessoa, M, Petta, S, Marques Souza de Oliveira, C, Prabhakaran, D, Pyrsopoulous, N, Rabiee, A, Ramji, A, Ratziu, V, Ravendhran, N, Ray, K, Roden, M, Romeo, S, Romero-Gomez, M, Rotman, Y, Rouabhia, S, Rowe, I, Sadirova, S, Alkhatry, M, Salupere, R, Satapathy, S, Schwimmer, J, Sebastiani, G, Seim, L, Seki, Y, Serme, A, Shapiro, D, Sharvadze, L, Shaw, J, Shawa, I, Shenoy, T, Shibolet, O, Shimakawa, Y, Shubrook, J, Singh, S, Sinkala, E, Skladany, L, Skrypnyk, I, Song, M, Sookoian, S, Sridharan, K, Stefan, N, Stine, J, Stratakis, N, Sheriff, D, Sundaram, S, Svegliati-Baroni, G, Swain, M, Tacke, F, Taheri, S, Tan, S, Tapper, E, Targher, G, Tcaciuc, E, Thiele, M, Tiniakos, D, Tolmane, I, Torre, A, Torres, E, Treeprasertsuk, S, Trenell, M, Turcan, S, Turcanu, A, Valantinas, J, van Kleef, L, Velarde Ruiz Velasco, J, Vesterhus, M, Vilar-Gomez, E, Waked, I, Wattacheril, J, Wedemeyer, H, Wilkins, F, Willemse, J, Wong, R, Yilmaz, Y, Yki-Jarvinen, H, Yu, M, Yumuk, V, Zeybel, M, Zheng, K, Zheng, M, Lazarus J. V., Mark H. E., Allen A. M., Arab J. P., Carrieri P., Noureddin M., Alazawi W., Alkhouri N., Alqahtani S. A., Arrese M., Bataller R., Berg T., Brennan P. N., Burra P., Castro-Narro G. E., Cortez-Pinto H., Cusi K., Dedes N., Duseja A., Francque S. M., Hagstrom H., Huang T. T. -K., Wajcman D. I., Kautz A., Kopka C. J., Krag A., Miller V., Newsome P. N., Rinella M. E., Romero D., Sarin S. K., Silva M., Spearman C. W., Tsochatzis E. A., Valenti L., Villota-Rivas M., Zelber-Sagi S., Schattenberg J. M., Wong V. W. -S., Younossi Z. M., Aberg F., Adams L., Al-Naamani K., Albadawy R. M., Alexa Z., Allison M., Alnaser F. A., Alswat K., Alvares-da-Silva M. R., Alvaro D., Alves-Bezerra M., Andrade R. J., Anstee Q. M., Awuku Y. A., Baatarkhuu O., Baffy G., Bakieva S., Bansal M. B., Barouki R., Batterham R. L., Behling C., Belfort-DeAguiar R., Berzigotti A., Betel M., Bianco C., Bosi E., Boursier J., Brunt E. M., Bugianesi E., Byrne C. J., Cabrera Cabrejos M. C., Caldwell S., Carr R., Castellanos Fernandez M. I., Castera L., Castillo-Lopez M. G., Caussy C., Cerda-Reyes E., Ceriello A., Chan W. -K., Chang Y., Charatcharoenwitthaya P., Chavez-Tapia N., Chung R. T., Colombo M., Coppell K., Cotrim H. P., Craxi A., Crespo J., Dassanayake A., Davidson N. O., De Knegt R., de Ledinghen V., Demir M., Desalegn H., Diago M., Dillon J. F., Dimmig B., Dirac M. A., Dirchwolf M., Dufour J. -F., Dvorak K., Ekstedt M., El-Kassas M., Elsanousi O. M., Elsharkawy A. M., Elwakil R., Eskridge W., Eslam M., Esmat G., Fan J. -G., Ferraz M. L., Flisiak R., Fortin D., Fouad Y., Freidman S. L., Fuchs M., Gadano A., Gastaldelli A., Geerts A., Geier A., George J., Gerber L. H., Ghazinyan H., Gheorghe L., Kile D. G., Girala M., Boon Bee G. G., Goossens N., Graupera I., Gronbaek H., Hamid S., Hebditch V., Henry Z., Hickman I. J., Hobbs L. A., Hocking S. L., Hofmann W. P., Idilman R., Iruzubieta P., Isaacs S., Isakov V. A., Ismail M. H., Jamal M. H., Jarvis H., Jepsen P., Jornayvaz F., Sudhamshu K. C., Kakizaki S., Karpen S., Kawaguchi T., Keating S. E., Khader Y., Kim S. U., Kim W., Kleiner D. E., Koek G., Joseph Komas N. P., Kondili L. A., Koot B. G., Korenjak M., Kotsiliti E., Koulla Y., Kugelmas C., Kugelmas M., Labidi A., Lange N. F., Lavine J. E., Lazo M., Leite N., Lin H. -C., Lkhagvaa U., Long M. T., Lopez-Jaramillo P., Lozano A., Macedo M. P., Malekzadeh R., Marchesini G., Marciano S., Martinez K., Martinez Vazquez S. E., Mateva L., Mato J. M., Nlombi C. M., McCary A. G., McIntyre J., McKee M., Mendive J. M., Mikolasevic I., Miller P. S., Milovanovic T., Milton T., Moreno-Alcantar R., Morgan T. R., Motala A., Muris J., Musso C., Nava-Gonzalez E. J., Negro F., Nersesov A. V., Neuschwander-Tetri B. A., Nikolova D., Norris S., Novak K., Ocama P., Ong J. P., Ong-Go A., Onyekwere C., Padilla M., Pais R., Pan C., Panduro A., Panigrahi M. K., Papatheodoridis G., Paruk I., Patel K., Goncalves C. P., Figueroa M. P., Perez-Escobar J., Pericas J. M., Perseghin G., Pessoa M. G., Petta S., Marques Souza de Oliveira C. P., Prabhakaran D., Pyrsopoulous N., Rabiee A., Ramji A., Ratziu V., Ravendhran N., Ray K., Roden M., Romeo S., Romero-Gomez M., Rotman Y., Rouabhia S., Rowe I. A., Sadirova S., Alkhatry M. S., Salupere R., Satapathy S. K., Schwimmer J. B., Sebastiani G., Seim L., Seki Y., Serme A. K., Shapiro D., Sharvadze L., Shaw J. E., Shawa I. T., Shenoy T., Shibolet O., Shimakawa Y., Shubrook J. H., Singh S. P., Sinkala E., Skladany L., Skrypnyk I., Song M. J., Sookoian S., Sridharan K., Stefan N., Stine J. G., Stratakis N., Sheriff D. S., Sundaram S. S., Svegliati-Baroni G., Swain M. G., Tacke F., Taheri S., Tan S. -S., Tapper E. B., Targher G., Tcaciuc E., Thiele M., Tiniakos D., Tolmane I., Torre A., Torres E. A., Treeprasertsuk S., Trenell M., Turcan S., Turcanu A., Valantinas J., van Kleef L. A., Velarde Ruiz Velasco J. A., Vesterhus M., Vilar-Gomez E., Waked I., Wattacheril J., Wedemeyer H., Wilkins F., Willemse J., Wong R. J., Yilmaz Y., Yki-Jarvinen H., Yu M. -L., Yumuk V., Zeybel M., Zheng K. I., and Zheng M. -H.

Abstract

Background & aims: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. Methods: Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. Results: The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had [removed]90% combined agreement. Conclusions: Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat. Impact and implications: An estimated 38% of adults and 13% o

Published
2023

26. P1117 Molecular and clinical characterization of metabolic associated steatotic liver disease in the setting of immune-mediated inflammatory diseases: a link with cancer risk in IBD?

Author

Rivas, C, primary, García-Nieto, E, additional, Rodríguez-Duque, J C, additional, García-Mateo, S, additional, Alonso Fernández, S, additional, Echavarria Rodriguez, V, additional, Iruzubieta, P, additional, García, M J, additional, Castro, B, additional, Armesto Alonso, S, additional, Rueda-Gotor, J, additional, González-Lopez, M, additional, Esteve-Codina, A, additional, Martínez-Dominguez, S, additional, García-Vaqué, J P, additional, Gomollón, F, additional, Crespo, J, additional, Rivero, M, additional, and Arias-Loste, M T, additional

Published
2024
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28. Silencing hepatic MCJ attenuates non-alcoholic fatty liver disease (NAFLD) by increasing mitochondrial fatty acid oxidation

Author

Barbier-Torres, Lucía, Fortner, Karen A., Iruzubieta, Paula, Delgado, Teresa C., Giddings, Emily, Chen, Youdinghuan, Champagne, Devin, Fernández-Ramos, David, Mestre, Daniela, Gomez-Santos, Beatriz, Varela-Rey, Marta, de Juan, Virginia Gutiérrez, Fernández-Tussy, Pablo, Zubiete-Franco, Imanol, García-Monzón, Carmelo, González-Rodríguez, Águeda, Oza, Dhaval, Valença-Pereira, Felipe, Fang, Qian, Crespo, Javier, Aspichueta, Patricia, Tremblay, Frederic, Christensen, Brock C., Anguita, Juan, Martínez-Chantar, María Luz, and Rincón, Mercedes

Published
2020
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32. Cenobamate in patients with highly refractory focal epilepsy: A retrospective real-world study.

Author

Beltrán-Corbellini, Álvaro, Romeral-Jiménez, María, Mayo, Pablo, Sánchez-Miranda Román, Irene, Iruzubieta, Pablo, Chico-García, Juan Luis, Parra-Díaz, Paloma, García-Morales, Irene, Toledano, Rafael, Aledo-Serrano, Ángel, and Gil-Nagel, Antonio

Abstract

• Cenobamate was effective and safe in a cohort of patients with highly refractory focal epilepsy. • The percentage of hyper-responder patients (> 90% of seizure reduction or seizure-free) was exceptionally high. • The introduction of cenobamate allowed the reduction of other concomitant ASM, particularly other sodium channel blockers, maintaining effectivity and reducing adverse events. To determine the effectiveness and safety outcomes of cenobamate in a cohort of patients with highly refractory focal epilepsy in routine clinical practice. Observational, retrospective, phase 4 study on subjects receiving cenobamate in three Spanish centers. The primary endpoint was the retention rate at the last follow-up. The main secondary endpoints were the 50%-responder and seizure-free rates at three months and the last follow-up. Other secondary endpoints were Global Clinical Impressions-Improvement (CGI-I) scores and treatment-emergent adverse events (TEAEs). Fifty-one patients with highly refractory focal epilepsy with 24.7 years of disease evolution, ten previously tried ASM, and a 23.5% of previous epilepsy surgery were included. The retention rate at the last follow-up was 80.4%. The 50% responder rate in focal seizures at three months was 56.5% (median reduction per month 51%, 0–74.6; p < 0.0001) and in focal to bilateral tonic-clonic seizures was 63.6% (median reduction per month 89%, 0–100; p = 0.022). A total of 54.3% of subjects reported a reduction in the intensity of focal seizures, and 66% manifested clinically significant satisfaction. Cenobamate allowed a significant decrease in concomitant ASM, especially sodium channel blockers. TEAEs were reported in 43.1% of individuals, 85% of whom resolved or improved, with no new safety findings. In this analysis of patients with highly refractory focal epilepsy treated with cenobamate according to standard clinical practice, there was evidence of a high reduction in both seizure frequency and intensity, with a manageable safety profile. [ABSTRACT FROM AUTHOR]

Published
2023
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34. No evidence of association between inherited thrombophilia and increased risk of liver fibrosis

Author

Ezcurra, Iranzu, Puente, Ángela, Cuadrado, Antonio, Tamayo, Ibai, Iruzubieta, Paula, Arias‐Loste, María Teresa, González, Francisco José, Pellón, Raúl, Sánchez, Sara, Crespo, Juan, Acebo, Mercedes, López‐Hoyos, Marcos, Pérez, Rocío, Cuesta, Amalia, Antón, Ángela, Echavarría, Víctor, Fábrega, Emilio, Crespo, Javier, and Fortea, Jose Ignacio

Abstract

Preliminary evidence suggests that inherited hypercoagulable disorders can lead to an increased risk of significant liver fibrosis. We aimed to investigate the prevalence of significant fibrosis in patients with inherited thrombophilia, assessed by using liver stiffness (LS), and to compare this prevalence to that found in a large population‐based cohort from the same region. This was a single‐center, cross‐sectional study. A complete laboratory analysis for liver disease, LS by transient elastography and an abdominal ultrasound were performed in patients with inherited thrombophilia diagnosed between May 2013‐February 2017. These patients were propensity score matched (ratio 1:4) with a population‐based cohort from the same region (PREVHEP‐ETHON study; NCT02749864; N= 5988). Of 241 patients with inherited thrombophilia, eight patients (3.3%) had significant fibrosis (LS ≥8 kPa). All of them had risk factors for liver disease and met diagnostic criteria for different liver diseases. After matching 221 patients with thrombophilia with 884 patients of the PREVHEP‐ETHON cohort, the prevalence of significant fibrosis was similar between both cohorts (1.8% vs. 3.6%, p= 0.488). Multivariate analysis showed that age and liver disease risk factors, but not belonging to the thrombophilia cohort, were associated with the presence of significant fibrosis. The magnitude of the increased risk of significant fibrosis in patients with risk factors for liver disease was also similar in both cohorts. Our findings do not provide evidence supporting an association between inherited thrombophilia and an increased risk of significant liver fibrosis, independent of the presence of liver‐related causes of fibrosis.

Published
2023
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35. Reperfusion therapy in acute ischaemic stroke due to cervical and cerebral artery dissection: Results from a Spanish multicentre study

Author

Campo-Caballero, D., primary, de la Riva, P., additional, de Arce, A., additional, Martínez-Zabaleta, M., additional, Rodríguez-Antigüedad, J., additional, Ekiza, J., additional, Iruzubieta, P., additional, Purroy, F., additional, Fuentes, B., additional, de Lera Alfonso, M., additional, Krupinski, J., additional, Mengual Chirife, J.J., additional, Palomeras, E., additional, Guisado-Alonso, D., additional, Rodríguez-Yáñez, M., additional, Ustrell, X., additional, Tejada García, J., additional, de Felipe Mimbrera, A., additional, Paré-Curell, M., additional, Tembl, J., additional, Cajaraville, S., additional, Garcés, M., additional, and Serena, J., additional

Published
2022
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36. Correction: Corrigendum: Hepatic p63 regulates steatosis via IKKβ/ER stress

Author

Porteiro, Begoña, Fondevila, Marcos F., Delgado, Teresa C., Iglesias, Cristina, Imbernon, Monica, Iruzubieta, Paula, Crespo, Javier, Zabala-Letona, Amaia, Fernø, Johan, González-Terán, Bárbara, Matesanz, Nuria, Hernández-Cosido, Lourdes, Marcos, Miguel, Tovar, Sulay, Vidal, Anxo, Sánchez-Ceinos, Julia, Malagon, Maria M., Pombo, Celia, Zalvide, Juan, Carracedo, Arkaitz, Buque, Xabier, Dieguez, Carlos, Sabio, Guadalupe, López, Miguel, Aspichueta, Patricia, Martínez-Chantar, María L., and Nogueiras, Ruben

Published
2017
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37. Frequency, Predictors, Etiology, and Outcomes for Deep Intracerebral Hemorrhage without Hypertension

Author

Prats-Sánchez L., Iruzubieta P., Vesperinas A., Collet R., Martínez-Domeño A., Guisado-Alonso D., Camps-Renom P., Delgado-Mederos R., Guasch-Jiménez M., Ramos-Pachón A., Rodríguez-Antigüedad J., Campo-Caballero D., Equiza J., de la Riva P., Martínez-Zabaleta M., de Arce A., and Martí-Fàbregas J.

Subjects
retrospective study, clinical outcome, thrombocytopenia, heparin, anticoagulant agent, middle aged, echocardiography, atrial fibrillation, nuclear magnetic resonance imaging, drug abuse, leukoaraiosis, antithrombocytic agent, neurological deficit score, aged, female, risk factor, brain angiography, frequency, diabetes mellitus, antihypertensive agent, brain hemorrhage, end stage liver disease, tertiary care center, adrenergic receptor stimulating agent, hospitalization, prospective study, hypertension, diagnostic imaging, alcohol consumption, brain, electrocardiography, congenital blood vessel malformation, tobacco use, electrocardiogram, Article, transthoracic echocardiography, male, blood clotting disorder, Rankin scale, ischemic stroke, follow up, controlled study, human, deterioration, dyslipidemia, international normalized ratio, platelet count, major clinical study, blood pressure monitoring, hospital discharge, age, treatment outcome
Abstract

Objectives: Some patients with deep intracerebral hemorrhage (ICH) have a transient hypertensive response and they may be erroneously classified as secondary to hypertension. We investigated frequency, risk factors, and outcomes for patients with deep ICH without hypertension. Materials and methods: We consecutively recruited patients with spontaneous ICH attending two Spanish stroke centers (January 2015-June 2019). Excluded were patients with lobar/infratentorial ICH and patients who died during hospitalization. We defined deep ICH without hypertension when the bleeding was in a deep structure, no requirement for antihypertensive agents during follow-up and no evident chronic hypertension markers evaluated by transthoracic echocardiography, 24 h ambulatory blood pressure monitoring and/or electrocardiography. We compared clinical, radiological, and 3-month functional outcome data for deep-ICH patients with hypertension versus those without hypertension. Results: Of 759 patients with ICH, 219 (mean age 69.6 ± 15.4 years, 54.8% men) met the inclusion criteria and 36 (16.4%) did not have hypertension. Of these 36 patients, 19 (52.7%) had a transient hypertensive response. Independent predictors of deep ICH without hypertension were age (adjusted OR:0.94;95%CI:0.91–0.96) and dyslipidemia (adjusted OR:0.27;95% CI:0.08–0.85). One third of deep ICH without hypertension were secondary to vascular malformations. Favorable outcomes (modified Rankin Scale 0–2) were more frequent in patients with deep ICH without hypertension compared to those with hypertension (70.9% vs 33.8%; p < 0.001). Conclusion: Of patients with deep ICH, 16.4% were unrelated with hypertension, around half showed hypertensive response, and around a third had vascular malformations. We suggest studying hypertension markers and performing a follow-up brain MRI in those patients with deep ICH without prior hypertension. © 2021 Elsevier Inc.

Published
2022
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38. Prevalence estimation of significant fibrosis because of NASH in Spain combining transient elastography and histology

Author

Calleja J, Rivera-Esteban J, Aller R, Hernandez-Conde M, Abad J, Pericas J, Benito H, Serra M, Escudero A, Ampuero J, Lucena A, Sanchez Y, Arias-Loste M, Iruzubieta P, Romero-Gomez M, Augustin S, and Crespo J

Subjects
hepatic fibrosis, non-alcoholic steatohepatitis, transient elastography, liver biopsy
Abstract

Background & Aims Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non-alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain. Methods This was an observational, retrospective, cross-sectional, population-based study with merged data from two Spanish datasets: a large (N = 12 246) population-based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi-centric biopsy-proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy-proven cohort. Results From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53-11.97) had a liver stiffness measurement (LSM) >= 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM >= 8 kPa because of NAFLD was 3.21% (95% CI 1.13-8.75). In the biopsy-proven NASH cohort, 389 patients had LSM >= 8 kPa. Among these, 37% did not have significant fibrosis (F2-4). The estimated prevalence of NASH F2-3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29-5.98) and 0.70% (95% CI 0.10-4.95) respectively. Conclusions These estimations provide an accurate picture of the current prevalence of NASH-related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available.

Published
2022

39. Not Available

Author

Gallego-Durán R, Albillos A, Ampuero J, Arechederra M, Bañares R, Blas-García A, Berná G, Caparrós E, Delgado TC, Falcón-Pérez JM, Francés R, Fernández-Barrena MG, Graupera I, Iruzubieta P, Nevzorova YA, Nogueiras R, Macías RI, Marín F, Sabio G, Soriano G, Vaquero J, Cubero FJ, and Gracia-Sancho J

Subjects
MASH, fibrosis, MAFLD, steatohepatitis, hepatocellular carcinoma
Abstract

This is a meeting report of the 3rd Translational Hepatology Meeting held in Alicante, Spain, in October 2021. The meeting, which was organized by the Spanish Association for the Study of the Liver (AEEH), provided an update on the recent advances in the field of basic and translational hepatology, with a particular focus on the molecular and cellular mechanisms and therapeutic targets involved in metabolic-associated fatty liver disease (MAFLD), metabolic-associated steatohepatitis (MASH), cirrhosis and end-stage hepatocellular carcinoma (HCC).

Published
2022

40. Prevalence of steatotic liver disease and steatohepatitis in a population of healthy workers.

Author

Guerra, P., Perez, J. Lopez, Cagnin, S., Iruzubieta, P., Pontisso, P., Martínez-Chantar, M.L., and Martini, A.

Abstract

Steatotic Liver Disease (SLD) may silently evolve into Steatohepatitis (SH). In clinical practice, elevation of liver enzymes (LE) is used as a surrogate marker of liver inflammation. Screening of liver disease is gaining attention and novel strategies need to be found. We aimed to study the prevalence and associated factors of SLD and SH in a population of healthy workers. 780 healthy workers were prospectively enrolled during yearly health checkups (from January to September 2024) at Bridgestone factory (Bilbao, Spain). Ultrasound, anthropometric and biochemical data were collected. 335 patients with all available data were further analysed. Patients were divided into the following groups: no steatosis and normal LE (Healthy), steatosis and normal LE (SLD), steatosis and elevated LE (SH), no steatosis and elevated LE (Hepatitis). The Healthy Group accounted for half of the patients (57%), while the remaining patients were divided into the other three groups (SLD 20%; SH 11%; Hepatitis 12%). The analysis of variance showed differences in age, BMI, HDL, triglycerides, glucose and haemoglobin. At post-hoc analysis only BMI increased significantly between Healthy (25.10 [23.15, 27.16]), SLD (26.87 [24.97, 30.05]) and SH Groups (30.38 [27.59, 33.18]). Multivariate logistic regression for risk factors for SLD showed: BMI (aOR 1.21 [1.11, 1.31], p < 0.001), and hypertension (aOR 2.19 [1.10, 4.37], p = 0.026). The only significant risk factor for SH after adjustment was BMI (aOR 1.31 [1.18, 1.48], p < 0.001). The inclusion of liver ultrasound and transaminases in healthy workers' checkups can be effective in identifying patients with metabolic liver disease. [ABSTRACT FROM AUTHOR]

Published
2025
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44. Physicians' Use of Digital Health Interventions in the Management of Nonalcoholic Fatty Liver Disease

Author

Lazarus, Jeffrey V., Villota-Rivas, Marcela, Jiménez-González, Carolina, Santos-Laso, Alvaro, Iruzubieta, Paula, Arias-Loste, María Teresa, Rice-Duek, Lisa, Leigh, Simon, Kopka, Christopher J., Turnes, Juan, Calleja, José Luis, and Crespo, Javier

Abstract

Globally, the use of digital health interventions (DHIs) is expanding, along with growing scientific evidence of their effectiveness. Given the high and increasing prevalence of noncommunicable liver disease, we surveyed 295 physicians across Spain about their knowledge, beliefs, attitudes, practices, and access with regard to DHIs for patient care and in particular for liver diseases, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Physicians reported high familiarity with DHIs, although most had not recommended them in patient care. Addressing concerns, including limited available time, evidence of effectiveness, education, training, and access may contribute to an increased uptake of these technologies.

Published
2023
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45. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

Author

Stephens, Camilla, primary, Robles-Diaz, Mercedes, additional, Medina-Caliz, Inmaculada, additional, Garcia-Cortes, Miren, additional, Ortega-Alonso, Aida, additional, Sanabria-Cabrera, Judith, additional, Gonzalez-Jimenez, Andres, additional, Alvarez-Alvarez, Ismael, additional, Slim, Mahmoud, additional, Jimenez-Perez, Miguel, additional, Gonzalez-Grande, Rocio, additional, Fernández, M. Carmen, additional, Casado, Marta, additional, Soriano, German, additional, Román, Eva, additional, Hallal, Hacibe, additional, Romero-Gomez, Manuel, additional, Castiella, Agustin, additional, Conde, Isabel, additional, Prieto, Martin, additional, Moreno-Planas, Jose Maria, additional, Giraldez, Alvaro, additional, Moreno-Sanfiel, J. Miguel, additional, Kaplowitz, Neil, additional, Lucena, M. Isabel, additional, Andrade, Raúl J., additional, Andrade, R.J., additional, Lucena, M.I., additional, Stephens, C., additional, Cortés, M. García, additional, Robles-Díaz, M., additional, Ortega-Alonso, A., additional, Pinazo, J., additional, Muñoz, B. García, additional, Alcántara, R., additional, Hernández, A., additional, Escaño, M.D. García, additional, del Campo, E., additional, Medina-Cáliz, I., additional, Sanabria-Cabrera, J., additional, González-Jiménez, A., additional, Sanjuán-Jiménez, R., additional, Cueto, A., additional, Álvarez-Álvarez, I., additional, Bonilla, E., additional, Di Zeo, D., additional, Niu, H., additional, Villanueva, M., additional, Papineau, A., additional, Pérez, M. Jiménez, additional, Grande, R. González, additional, Ortega, S. López, additional, Santaella, I., additional, Ocaña, A., additional, Palomino, P., additional, Fernández, M.C., additional, Peláez, G., additional, Porcel, A., additional, Casado, M., additional, Sánchez, M. González, additional, Romero-Gómez, M., additional, Millán-Domínguez, R., additional, Fombuena, B., additional, Gallego, R., additional, Ampuero, J., additional, Campo, J.A. del, additional, Calle-Sanz, R., additional, Rojas, L., additional, Rojas, A., additional, Gómez, A. Gil, additional, Vilar, E., additional, Soriano, G., additional, Guarner, C., additional, Román, E.M., additional, Manuitt, M.A. Quijada, additional, Arbos, R.M. Antonijoan, additional, Delgado, J. Sánchez, additional, Gómez, M. Vergara, additional, Hallal, H., additional, Oltra, E. García, additional, Arcos, J.C. Titos, additional, Martínez, A. Pérez, additional, Cobarro, C. Sánchez, additional, Caparrós, J.M. Egea, additional, Castiella, A., additional, Zapata, E., additional, Arenas, J., additional, García, A. Gómez, additional, Esandi, F.J., additional, Blanco, S., additional, Odriozola, P. Martínez, additional, Crespo, J., additional, Iruzubieta, P., additional, Cabezas, J., additional, Gallego, A. Giráldez, additional, Rodríguez Seguel, E. del P., additional, Cuaresma, M., additional, Gallego, J. González, additional, Jorquera, F., additional, Campos, S. Sánchez, additional, Otazua, P., additional, de Juan Gómez, A., additional, Salmerón, J., additional, Gila, A., additional, Quiles, R., additional, González, J.M., additional, Lorenzo, S., additional, Prieto, M., additional, Amiel, I. Conde, additional, Berenguer, M., additional, García-Eliz, M., additional, Primo, J., additional, Molés, J.R., additional, Garayoa, A., additional, Carrascosa, M., additional, Domínguez, E. Gómez, additional, Cuevas, L., additional, Farré, M., additional, Montané, E., additional, Barriocanal, A.M., additional, Arellano, A.L., additional, Sanz, Y., additional, Morillas, R.M., additional, Sala, M., additional, Ridaura, H. Masnou, additional, Bruguera, M., additional, Gines, P., additional, Lens, S., additional, García, J.C., additional, Mariño, Z., additional, Guerra, M. Hernández, additional, Sanfiel, J.M. Moreno, additional, Fernández del Campo, C. Boada, additional, Tejedor, M., additional, Ferrer, R. González, additional, Fernández, C., additional, Gil, M. Fernández, additional, Montero, J.L., additional, Mata, M. de la, additional, Olmo, J. Fuentes, additional, Bonilla, E.M. Fernández, additional, Moreno, J.M., additional, Martínez-Rodenas, P., additional, Garrido, M., additional, Oliva, C., additional, Rendón, P., additional, Samaniego, J. García, additional, Madejón, A., additional, Calleja, J.L., additional, Porras, J.L. Martínez, additional, Cabriada, J.L., additional, Pérez-Moreno, J.M., additional, and Lara, C., additional

Published
2021
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46. Reperfusion treatment in acute ischaemic stroke due to cervical and cerebral artery dissection: results of a Spanish national multicentre study

Author

Campo-Caballero D, de la Riva P, de Arce A, Martínez-Zabaleta M, Rodríguez-Antigüedad J, Ekiza J, Iruzubieta P, Purroy F, Fuentes B, de Lera Alfonso M, Krupinski J, Mengual Chirife JJ, Palomeras E, Guisado-Alonso D, Rodríguez-Yáñez M, Ustrell X, Tejada García J, de Felipe Mimbrera A, Paré-Curell M, Tembl J, Cajaraville S, Garcés M, and Serena J

Subjects
Disección, Dissection, Fibrinolysis, Fibrinólisis, Ictus, Reperfusion, Reperfusión, Stroke, Thrombectomy, Trombectomía, cardiovascular diseases
Abstract

Ischaemic stroke (IS) due to cervical and cerebral artery dissection (CAD) is a rare entity, and few data are available on the use of such reperfusion therapies as intravenous fibrinolysis and mechanical thrombectomy in these patients. We analysed the use of these treatments in patients with IS due to CAD and compared them against patients receiving reperfusion treatment for IS of other aetiologies.We conducted an observational, retrospective, multicentre study of patients with IS due to CAD recorded in the National Stroke Registry of the Spanish Society of Neurology during the period 2011-2019. Comparative analyses were performed between: a) patients with CAD treated and not treated with reperfusion therapies and b) patients treated with reperfusion for IS due to CAD and patients treated with reperfusion for IS due to other causes. Epidemiological data, stroke variables, and outcomes at discharge and at 3 months were included in the analysis.The study included 21,037 patients with IS: 223 (1%) had IS due to CAD, of whom 68 (30%) received reperfusion treatment. Reperfusion treatments were used less frequently in cases of vertebral artery dissection and more frequently in patients with carotid artery occlusion. Compared to patients with IS due to other causes, patients with CAD were younger, more frequently underwent mechanical thrombectomy, and less frequently received intravenous fibrinolysis. Rates of haemorrhagic complications, mortality, and independence at 3 months were similar in both groups.Reperfusion therapy is frequently used in patients with IS due to CAD. The outcomes of these patients demonstrate the efficacy and safety of reperfusion treatments, and are comparable to the outcomes of patients with IS due to other aetiologies.

Published
2020

47. Targeting Hepatic Glutaminase 1 Ameliorates Non-alcoholic Steatohepatitis by Restoring Very-Low-Density Lipoprotein Triglyceride Assembly

Author

Simon J, Nuñez-García M, Fernández-Tussy P, Barbier-Torres L, Fernández-Ramos D, Gómez-Santos B, Buqué X, Lopitz-Otsoa F, Goikoetxea-Usandizaga N, Serrano-Macia M, Rodriguez-Agudo R, Bizkarguenaga M, Zubiete-Franco I, Gutiérrez-de Juan V, Cabrera D, Alonso C, Iruzubieta P, Romero-Gomez M, van Liempd S, Castro A, Nogueiras R, Varela-Rey M, Falcón-Pérez JM, Villa E, Crespo J, Lu SC, Mato JM, Aspichueta P, Delgado TC, Martínez-Chantar ML.

Abstract

SUMMARY Non-alcoholic steatohepatitis (NASH) is characterized by the accumulation of hepatic fat in an inflammatory/fibrotic background. Herein, we show that the hepatic high-activity glutaminase 1 isoform (GLS1) is overexpressed in NASH. Importantly, GLS1 inhibition reduces lipid content in choline and/or methionine deprivation-induced steatotic mouse primary hepatocytes, in human hepatocyte cell lines, and in NASH mouse livers. We suggest that under these circumstances, defective glutamine fueling of anaplerotic mitochondrial metabolism and concomitant reduction of oxidative stress promotes a reprogramming of serine metabolism, wherein serine is shifted from the generation of the antioxidant glutathione and channeled to provide one-carbon units to regenerate the methionine cycle. The restored methionine cycle can induce phosphatidylcholine synthesis from the phosphatidylethanolamine N-methyltransferasemediated and CDP-choline pathways as well as by base-exchange reactions between phospholipids, thereby restoring hepatic phosphatidylcholine content and very-low-density lipoprotein export. Overall, we provide evidence that hepatic GLS1 targeting is a valuable therapeutic approach in NASH.

Published
2020
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49. Cathepsin D is essential for the degradomic shift of macrophages required to resolve liver fibrosis.

Author

Ruiz-Blázquez, Paloma, Fernández-Fernández, María, Pistorio, Valeria, Martinez-Sanchez, Celia, Costanzo, Michele, Iruzubieta, Paula, Zhuravleva, Ekaterina, Cacho-Pujol, Júlia, Ariño, Silvia, Del Castillo-Cruz, Alejandro, Núñez, Susana, Andersen, Jesper B., Ruoppolo, Margherita, Crespo, Javier, García-Ruiz, Carmen, Pavone, Luigi Michele, Reinheckel, Thomas, Sancho-Bru, Pau, Coll, Mar, and Fernández-Checa, José C.

Abstract

Fibrosis contributes to 45% of deaths in industrialized nations and is characterized by an abnormal accumulation of extracellular matrix (ECM). There are no specific anti-fibrotic treatments for liver fibrosis, and previous unsuccessful attempts at drug development have focused on preventing ECM deposition. Because liver fibrosis is largely acknowledged to be reversible, regulating fibrosis resolution could offer novel therapeutical options. However, little is known about the mechanisms controlling ECM remodeling during resolution. Changes in proteolytic activity are essential for ECM homeostasis and macrophages are an important source of proteases. Herein, in this study we evaluate the role of macrophage-derived cathepsin D (CtsD) during liver fibrosis. CtsD expression and associated pathways were characterized in single-cell RNA sequencing and transcriptomic datasets in human cirrhosis. Liver fibrosis progression, reversion and functional characterization were assessed in novel myeloid-CtsD and hepatocyte-CtsD knock-out mice. Analysis of single-cell RNA sequencing datasets demonstrated CtsD was expressed in macrophages and hepatocytes in human cirrhosis. Liver fibrosis progression, reversion and functional characterization were assessed in novel myeloid-CtsD (CtsDΔMyel) and hepatocyte-CtsD knock-out mice. CtsD deletion in macrophages, but not in hepatocytes, resulted in enhanced liver fibrosis. Both inflammatory and matrisome proteomic signatures were enriched in fibrotic CtsDΔMyel livers. Besides, CtsDΔMyel liver macrophages displayed functional, phenotypical and secretomic changes, which resulted in a degradomic phenotypical shift, responsible for the defective proteolytic processing of collagen I in vitro and impaired collagen remodeling during fibrosis resolution in vivo. Finally, CtsD-expressing mononuclear phagocytes of cirrhotic human livers were enriched in lysosomal and ECM degradative signaling pathways. Our work describes for the first-time CtsD-driven lysosomal activity as a central hub for restorative macrophage function during fibrosis resolution and opens new avenues to explore their degradome landscape to inform drug development. [Display omitted] • Human cirrhotic CtsD-expressing macrophages are enriched in ECM degradative pathways. • Myeloid-CtsD KO mice present enhanced liver fibrosis and impaired resolution. • CtsD contributes to functional, phenotypical and secretomic changes in macrophages. • CtsD-driven macrophage degradomic shift is essential for fibrosis resolution. [ABSTRACT FROM AUTHOR]

Published
2024
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50. Clinical Characteristics and Outcome of Drug‐Induced Liver Injury in the Older Patients: From the Young‐Old to the Oldest‐Old

Author

Weersink, Rianne A., primary, Alvarez‐Alvarez, Ismael, additional, Medina‐Cáliz, Inmaculada, additional, Sanabria‐Cabrera, Judith, additional, Robles‐Díaz, Mercedes, additional, Ortega‐Alonso, Aida, additional, García‐Cortés, Miren, additional, Bonilla, Elvira, additional, Niu, Hao, additional, Soriano, German, additional, Jimenez‐Perez, Miguel, additional, Hallal, Hacibe, additional, Blanco, Sonia, additional, Kaplowitz, Neil, additional, Lucena, M. Isabel, additional, Andrade, Raúl J., additional, Andrade, R.J., additional, Lucena, M.I., additional, Stephens, C., additional, García Cortés, M., additional, Robles Díaz, M., additional, Ortega Alonso, A., additional, Pinazo, J., additional, García Muñoz, B., additional, Alcántara, R., additional, Hernández, A., additional, García‐Escaño, M.D., additional, Medina‐Cáliz, I., additional, Sanabria‐Cabrera, J., additional, Alvarez‐Alvarez, I., additional, Bonilla, E., additional, Niu, H., additional, Di‐Zeo, D., additional, Del Campo, E., additional, Jiménez Pérez, M., additional, González Grande, R., additional, López Ortega, S., additional, Santaella, I., additional, Ocaña, A., additional, Palomino, P., additional, Fernández, M.C., additional, Porcel, A., additional, Casado, M., additional, González Sánchez, M., additional, Romero‐Gómez, M., additional, Millán‐Domínguez, R., additional, Fombuena, B., additional, Gallego, R., additional, Ampuero, J., additional, del Campo, J.A., additional, Calle‐Sanz, R., additional, Rojas, L., additional, Rojas, A., additional, Gil Gómez, A., additional, Vilar, E., additional, Soriano, G., additional, Guarner, C., additional, Román, E.M., additional, Quijada Manuitt, M.A., additional, Antonijoan Arbos, R.M., additional, Farré, M., additional, Montané, E., additional, Arellano, A.L., additional, Barriocanal, A.M., additional, Sanz, Y., additional, Morillas, R.M., additional, Sala, M., additional, Masnou Ridaura, H., additional, Sánchez Delgado, J., additional, Vergara Gómez, M., additional, Hallal, H., additional, García Oltra, E., additional, Titos Arcos, J.C., additional, Pérez Martínez, A., additional, Sánchez Cobarro, C., additional, Egea Caparrós, J.M., additional, Castiella, A., additional, Arenas, J., additional, Gomez Osua, M.I., additional, Gómez García, A., additional, Esandi, F.J., additional, Blanco, S., additional, Martínez Odriozola, P., additional, Crespo, J., additional, Iruzubieta, P., additional, Cabezas, J., additional, Giráldez Gallego, A., additional, Rodríguez Seguel, E. del P., additional, Cuaresma, M., additional, Prieto, M., additional, Conde Amiel, I., additional, Berenguer, M., additional, García‐Eliz, M., additional, Moreno, J.M., additional, Martínez‐Rodenas, P., additional, Garrido, M., additional, Oliva, C., additional, Gómez Domínguez, E., additional, Cabrera, L., additional, Cuevas, L., additional, Bruguera, M., additional, Gines, P., additional, Lens, S., additional, García, J.C., additional, Mariño, Z., additional, Hernández Guerra, M., additional, Moreno San Fiel, M., additional, Boada Fernández del Campo, C., additional, Fuentes Olmo, J., additional, Fernández Bonilla, E.M., additional, Jorquera, F., additional, and González Gallego, J., additional

Published
2020
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