Browsing by Author "Banales, Jesus M."

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    Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles
    (2022) Martinez-Arranz, Ibon; Bruzzone, Chiara; Noureddin, Mazen; Gil-Redondo, Ruben; Minchole, Itziar; Bizkarguenaga, Maider; Arretxe, Enara; Iruarrizaga-Lejarreta, Marta; Fernandez-Ramos, David; Lopitz-Otsoa, Fernando; Mayo, Rebeca; Embade, Nieves; Newberry, Elizabeth; Mittendorf, Bettina; Izquierdo-Sanchez, Laura; Smid, Vaclav; Arnold, Jorge; Iruzubieta, Paula; Perez Castano, Ylenia; Krawczyk, Marcin; Marigorta, Urko M.; Morrison, Martine C.; Kleemann, Robert; Martin-Duce, Antonio; Hayardeny, Liat; Vitek, Libor; Bruha, Radan; Aller de la Fuente, Rocio; 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; Mato, Jose M.
    Background and Aims We 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 Results We 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. Conclusions Metabolomic 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.
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    Serum identification of at-risk MASH: The metabolomics-advanced steatohepatitis fibrosis score (MASEF)
    (2024) Noureddin, Mazen; Truong, Emily; Mayo, Rebeca; Martinez-Arranz, Ibon; Banales, Jesus M.; Minchole, Itziar; Arrese, Marco; Cusi, Kenneth; Arias-Loste, Maria Teresa; Bruha, Radan; Romero-Gomez, Manuel; Iruzubieta, Paula; Aller, Rocio; Ampuero, Javier; Calleja, Jose Luis; Ibanez-Samaniego, Luis; Aspichueta, Patricia; Martin-Duce, Antonio; Kushner, Tatyana; Ortiz, Pablo; Harrison, Stephen A.; Anstee, Quentin M.; Crespo, Javier; Mato, Jose M.; Sanyal, Arun J.
    Background: Early identification of those with NAFLD activity score >= 4 and significant fibrosis (>= F2) or at-risk metabolic dysfunction-associated steatohepatitis (MASH) is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH.
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    The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma
    (2021) Lewinska, Monika; Santos-Laso, Alvaro; Arretxe, Enara; Alonso, Cristina; Zhuravleva, Ekaterina; Jimenez-Aguero, Raul; Eizaguirre, Emma; Jesus Pareja, Maria; Romero-Gomez, Manuel; Arrese, Marco; Suppli, Malte P.; Knop, Filip K.; Oversoe, Stine Karlsen; Villadsen, Gerda Elisabeth; Decaens, Thomas; Carrilho, Flair Jose; de Oliveira, Claudia P. M. S.; Sangro, Bruno; Macias, Rocio I. R.; Banales, Jesus M.; Andersen, Jesper B.
    Background: Non-alcoholic fatty liver disease (NAFLD) is affecting more people globally. Indeed, NAFLD is a spectrum of metabolic dysfunctions that can progress to hepatocellular carcinoma (NAFLD-HCC). This development can occur in a non-cirrhotic liver and thus, often lack clinical surveillance. The aim of this study was to develop non-invasive surveillance method for NAFLD-HCC.