Raquel

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    Abnormal Liver Function Test in Patients Infected with Coronavirus (SARS-CoV-2): A Retrospective Single-Center Study from Spain
    (2021) Bañares, R. (Rafael); Raquel; Nevzorova, Y. (Yulia); Avila, M.A. (Matías Antonio); Estévez-Vázquez, O. (Olga); Flores-Perojo, V. (Vicente); Ruiz-Margáin, A. (Astrid); Martínez-Naves, E. (Eduardo); Trautwein, C. (Christian); Bosch, J. (Jaume); Cubero, F.J. (Francisco Javier); Regueiro, J.R. (José Ramón); Macías-Rodríguez, R.U. (Ricardo U.)
    The outbreak of the novel coronavirus SARS-CoV-2 epidemic has rapidly spread and still poses a serious threat to healthcare systems worldwide. In the present study, electronic medical records containing clinical indicators related to liver injury in 799 COVID-19-confirmed patients admitted to a hospital in Madrid (Spain) were extracted and analyzed. Correlation between liver injury and disease outcome was also evaluated. Serum levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyltransferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and AST/ALT ratio were elevated above the Upper Limit of Normal (ULN) in 25.73%, 49.17%, 34.62%, 24.21%, 55.84% and 75% of patients, respectively. Interestingly, significant positive correlation between LDH levels and the AST/ALT ratio with disease outcome was found. Our data showed that SARS-CoV-2 virus infection leads to mild, but significant changes in serum markers of liver injury. The upregulated LDH levels as well as AST/ALT ratios upon admission may be used as additional diagnostic characteristic for COVID-19 patients.
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    An experimental DUAL model of advanced liver damage
    (2021) Bañares, R. (Rafael); Asensio, I. (Iris); Guo, F. (Feifei); Raquel; Singh, Y. (Youvika); Nevzorova, Y. (Yulia); Nakaya, H.I. (Helder I.); Ampuero, J. (Javier); Gómez, M. (Manuel); Peligros, M.I. (María Isabel); Avila, M.A. (Matías Antonio); Estévez-Vázquez, O. (Olga); López-Alcántara, N. (Nuria); Juárez, I. (Ignacio); Reissing, J. (Johanna); Liedtke, C. (Christian); Morán, L. (Laura); Santamaría, E. (Eva); Lamas-Paz, A. (Arantxa); Trautwein, C. (Christian); Vaquero, J. (Javier); Haas, U. (Ute); Martín-Villa, J.M. (José Manuel); Woitok, M.M. (Marius Maximilian); Bataller, R. (Ramón); Mazariegos, M.S. (Marina S.); Gómez-del-Moral, M. (Manuel); Zheng, K. (Kang); Bruns, T. (Tony); Cubero, F.J. (Francisco Javier); Argemí, J. (Josepmaria); Chen, C. (Chaobo)
    Individuals exhibiting an intermediate alcohol drinking pattern in conjunction with signs of metabolic risk present clinical features of both alcohol-associated and metabolic-associated fatty liver diseases. However, such combination remains an unexplored area of great interest, given the increasing number of patients affected. In the present study, we aimed to develop a preclinical DUAL (alcohol-associated liver disease plus metabolic-associated fatty liver disease) model in mice. C57BL/6 mice received 10% vol/vol alcohol in sweetened drinking water in combination with a Western diet for 10, 23, and 52 weeks (DUAL model). Animals fed with DUAL diet elicited a significant increase in body mass index accompanied by a pronounced hypertrophy of adipocytes, hypercholesterolemia, and hyperglycemia. Significant liver damage was characterized by elevated plasma alanine aminotransferase and lactate dehydrogenase levels, extensive hepatomegaly, hepatocyte enlargement, ballooning, steatosis, hepatic cell death, and compensatory proliferation. Notably, DUAL animals developed lobular inflammation and advanced hepatic fibrosis. Sequentially, bridging cirrhotic changes were frequently observed after 12 months. Bulk RNA-sequencing analysis indicated that dysregulated molecular pathways in DUAL mice were similar to those of patients with steatohepatitis. Conclusion: Our DUAL model is characterized by obesity, glucose intolerance, liver damage, prominent steatohepatitis and fibrosis, as well as inflammation and fibrosis in white adipose tissue. Altogether, the DUAL model mimics all histological, metabolic, and transcriptomic gene signatures of human advanced steatohepatitis, and therefore serves as a preclinical tool for the development of therapeutic targets.