Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study
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Le résumé fourni par la source
Background Insights into the mechanisms driving metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLHIV) remain limited. Plasma proteomics holds promise for biomarker discovery and the elucidation of biological mechanisms. Methods We performed cross-sectional analyses on data from 1036 virally suppressed PLHIV using antiretroviral treatment (ART) from the Dutch multi-centre 2000HIV cohort. Participants underwent transient elastography to assess liver steatosis (controlled attenuation parameter (CAP) ≥263 dB/m) and -fibrosis (liver stiffness measurement (LSM) ≥7.0 kPa). Plasma protein concentrations (n = 2367) (Olink® Explore Panel) were compared between PLHIV with vs. without liver steatosis and PLHIV with vs. without fibrosis. Enriched pathways (using GO, KEGG and Reactome libraries) and correlations with clinical characteristics were assessed, and analyses were stratified by BMI category. In addition, concentrations of 242 proteins were compared between individuals ("controls") with and without liver steatosis (ratio of methylene:methylene and water >5.6% on magnetic resonance spectroscopy) from a separate cohort (300-OB), all having a BMI >26 kg/m 2 . Findings Steatosis and fibrosis were associated with 67/2367 (2.2%) and 17/2367 (0.7%) differentially expressed proteins (DEP), respectively, enriched in mostly metabolic pathways. Immunoglobulin superfamily member 9 (IGSF9) was amongst the top DEP associated with both steatosis and fibrosis. Stratifying by BMI revealed 8/2367 DEP associated with steatosis in lean- and 12/2367 DEP in overweight/obese individuals, with two shared DEP (IGSF9 and GHR). Conversely, protein signatures of overweight/obese PLHIV (32/242 DEP) and overweight/obese HIV-uninfected individuals (32/242 DEP) exhibited substantial overlap with 16 shared DEP. Notably, DEP correlated with HIV characteristics in lean individuals but not in overweight/obese PLHIV. Interpretation Lean and overweight/obese PLHIV exhibit distinct proteomic signatures associated with liver steatosis, with the former being more strongly correlated with HIV-specific factors and ART. In addition, we identified a protein, IGSF9, strongly related to liver fibrosis and steatosis across BMI categories. Funding The 2000HIV study is funded by ViiV Healthcare.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study
- Date Crossref
- 01/11/2024
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Radboud University Nijmegen pays non établi dans la noticeUniversité ou école supérieure
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Radboud University Medical Center pays non établi dans la noticeOrganisme public
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Erasmus MC pays non établi dans la noticeÉtablissement de santé
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Erasmus University Rotterdam pays non établi dans la noticeUniversité ou école supérieure
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OLVG pays non établi dans la noticeÉtablissement de santé
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Iuliu Hațieganu University of Medicine and Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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Radboud University Medical Centre Department of Internal Medicine pays non établi dans la noticeUniversité ou école supérieure
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Department of Medical Microbiology and Infectious Diseases pays non établi dans la noticeInstitution
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Department of Internal Medicine pays non établi dans la noticeInstitution
Radboud University Nijmegen, Radboud University Medical Center et Erasmus MC, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.