Articles producció científica> Enginyeria Electrònica, Elèctrica i Automàtica

Untargeted lipidomics uncovers lipid signatures that distinguish severe from moderate forms of acutely decompensated cirrhosis

  • Identification data

    Identifier: imarina:9231293
    Authors:
    Claria, JoanCurto, AnnaMoreau, RichardColsch, BenoitLopez-Vicario, CristinaLozano, Juan JoseAguilar, FerranCastelli, Florence AFenaille, FrancoisJunot, ChristopheZhang, IngridVinaixa, MariaYanes, OscarCaraceni, PaoloTrebicka, JonelFernandez, JavierAngeli, PaoloJalan, RajivArroyo, Vicente
    Abstract:
    Background & Aims: Acute decompensation (AD) of cirrhosis is a heterogeneous clinical entity associated with moderate mortality. In some patients, this condition develops quickly into the more deadly acute-on-chronic liver failure (ACLF), in which other organs such as the kidneys or brain fail. The aim of this study was to characterize the blood lipidome in a large series of patients with cirrhosis and identify specific signatures associated with AD and ACLF development. Methods: Serum untargeted lipidomics was performed in 561 patients with AD (518 without and 43 with ACLF) (discovery cohort) and in 265 patients with AD (128 without and 137 with ACLF) in whom serum samples were available to perform repeated measurements during the 28-day follow-up (validation cohort). Analyses were also performed in 78 patients with AD included in a therapeutic albumin trial (43 patients with compensated cirrhosis and 29 healthy individuals). Results: The circulating lipid landscape associated with cirrhosis was characterized by a generalized suppression, which was more manifest during AD and in non-surviving patients. By computing discriminating accuracy and the variable importance projection score for each of the 223 annotated lipids, we identified a sphingomyelin fingerprint specific for AD of cirrhosis and a distinct cholesteryl ester and lysophosphatidylcholine finger-print for ACLF. Liver dysfunction and infections were the prin-cipal net contributors to these fingerprints, which were dynamic and interchangeable between patients with AD whose condition worsened to ACLF and those who improved. Notably, blood lysophosphatidylcholine levels increased in these patients after albumin therapy. Conclusions: Our findings provide insights into the lipid land-scape associated with decompen
  • Others:

    Author, as appears in the article.: Claria, Joan; Curto, Anna; Moreau, Richard; Colsch, Benoit; Lopez-Vicario, Cristina; Lozano, Juan Jose; Aguilar, Ferran; Castelli, Florence A; Fenaille, Francois; Junot, Christophe; Zhang, Ingrid; Vinaixa, Maria; Yanes, Oscar; Caraceni, Paolo; Trebicka, Jonel; Fernandez, Javier; Angeli, Paolo; Jalan, Rajiv; Arroyo, Vicente
    Department: Enginyeria Electrònica, Elèctrica i Automàtica
    URV's Author/s: Vinaixa Crevillent, Maria / Yanes Torrado, Óscar
    Keywords: Systemic inflammation Survival Sphingosine 1 phosphate Sphingomyelin Sphingolipid Phosphatidylcholine sterol acyltransferase Phosphatidylcholine Pathophysiology Palmitoleic acid Organ failures Or-gan failures Omega 3 fatty acid Monounsaturated fatty acid Middle aged Male Major clinical study Lysophosphatidylcholine Liver dysfunction Liquid chromatography-mass spectrometry Lipids Lipidomics Lipidome Lipid metabolism Lipid homeostasis Lipid fingerprinting Lipid blood level Immune response Icosapentaenoic acid Human serum albumin Human Hepatitis Follow up Female Docosahexaenoic acid Disease severity Disease course Disease association Disease Decompensated liver cirrhosis Decompensated cirrhosis Cytokine Controlled study Cohort analysis Cholesterol ester Ceramide C reactive protein Blood sampling Article Adult Acute on chronic liver failure Acute disease
    Abstract: Background & Aims: Acute decompensation (AD) of cirrhosis is a heterogeneous clinical entity associated with moderate mortality. In some patients, this condition develops quickly into the more deadly acute-on-chronic liver failure (ACLF), in which other organs such as the kidneys or brain fail. The aim of this study was to characterize the blood lipidome in a large series of patients with cirrhosis and identify specific signatures associated with AD and ACLF development. Methods: Serum untargeted lipidomics was performed in 561 patients with AD (518 without and 43 with ACLF) (discovery cohort) and in 265 patients with AD (128 without and 137 with ACLF) in whom serum samples were available to perform repeated measurements during the 28-day follow-up (validation cohort). Analyses were also performed in 78 patients with AD included in a therapeutic albumin trial (43 patients with compensated cirrhosis and 29 healthy individuals). Results: The circulating lipid landscape associated with cirrhosis was characterized by a generalized suppression, which was more manifest during AD and in non-surviving patients. By computing discriminating accuracy and the variable importance projection score for each of the 223 annotated lipids, we identified a sphingomyelin fingerprint specific for AD of cirrhosis and a distinct cholesteryl ester and lysophosphatidylcholine finger-print for ACLF. Liver dysfunction and infections were the prin-cipal net contributors to these fingerprints, which were dynamic and interchangeable between patients with AD whose condition worsened to ACLF and those who improved. Notably, blood lysophosphatidylcholine levels increased in these patients after albumin therapy. Conclusions: Our findings provide insights into the lipid land-scape associated with decompensation of cirrhosis and ACLF progression and identify unique non-invasive diagnostic bio-markers of advanced cirrhosis. Lay summary: Analysis of lipids in blood from patients with advanced cirrhosis reveals a general suppression of their levels in the circulation of these patients. A specific group of lipids known as sphingomyelins are useful to distinguish between patients with compensated and decompensated cirrhosis. Another group of lipids designated cholesteryl esters further distinguishes patients with decompensated cirrhosis who are at risk of developing organ failures. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
    Thematic Areas: Química Medicina ii Medicina i Interdisciplinar Hepatology General medicine Gastroenterology & hepatology Engenharias iv Engenharias ii Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: maria.vinaixa@urv.cat oscar.yanes@urv.cat maria.vinaixa@urv.cat
    Author identifier: 0000-0001-9804-0171 0000-0003-3695-7157 0000-0001-9804-0171
    Record's date: 2024-10-12
    Papper version: info:eu-repo/semantics/publishedVersion
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Journal Of Hepatology. 75 (5): 1116-1127
    APA: Claria, Joan; Curto, Anna; Moreau, Richard; Colsch, Benoit; Lopez-Vicario, Cristina; Lozano, Juan Jose; Aguilar, Ferran; Castelli, Florence A; Fenaill (2021). Untargeted lipidomics uncovers lipid signatures that distinguish severe from moderate forms of acutely decompensated cirrhosis. Journal Of Hepatology, 75(5), 1116-1127. DOI: 10.1016/j.jhep.2021.06.043
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2021
    Publication Type: Journal Publications
  • Keywords:

    Gastroenterology & Hepatology,Hepatology
    Systemic inflammation
    Survival
    Sphingosine 1 phosphate
    Sphingomyelin
    Sphingolipid
    Phosphatidylcholine sterol acyltransferase
    Phosphatidylcholine
    Pathophysiology
    Palmitoleic acid
    Organ failures
    Or-gan failures
    Omega 3 fatty acid
    Monounsaturated fatty acid
    Middle aged
    Male
    Major clinical study
    Lysophosphatidylcholine
    Liver dysfunction
    Liquid chromatography-mass spectrometry
    Lipids
    Lipidomics
    Lipidome
    Lipid metabolism
    Lipid homeostasis
    Lipid fingerprinting
    Lipid blood level
    Immune response
    Icosapentaenoic acid
    Human serum albumin
    Human
    Hepatitis
    Follow up
    Female
    Docosahexaenoic acid
    Disease severity
    Disease course
    Disease association
    Disease
    Decompensated liver cirrhosis
    Decompensated cirrhosis
    Cytokine
    Controlled study
    Cohort analysis
    Cholesterol ester
    Ceramide
    C reactive protein
    Blood sampling
    Article
    Adult
    Acute on chronic liver failure
    Acute disease
    Química
    Medicina ii
    Medicina i
    Interdisciplinar
    Hepatology
    General medicine
    Gastroenterology & hepatology
    Engenharias iv
    Engenharias ii
    Educação física
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Biotecnología
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