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Nonalcoholic fatty liver disease (NAFLD) severity is associated to a nonhemostatic contribution and proinflammatory phenotype of platelets.

Authors
  • Miele, Luca1
  • Alberelli, Maria Adele2
  • Martini, Maurizio3
  • Liguori, Antonio4
  • Marrone, Giuseppe4
  • Cocomazzi, Alessandra5
  • Vecchio, Fabio Maria5
  • Landolfi, Raffaele6
  • Gasbarrini, Antonio6
  • Grieco, Antonio6
  • De Candia, Erica7
  • 1 Unità di Medicina Interna e del Trapianto di Fegato, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del S. Cuore, Roma, Italy. Electronic address: [email protected] , (Italy)
  • 2 UOSD Malattie Emorragiche e Trombotiche, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy. , (Italy)
  • 3 Dipartimento di Scienze della vita e sanità pubblica, Università Cattolica del S. Cuore, Roma, Italy; UOC Anatomia Patologica, Dipartimento di scienze della salute della donna, del bambino e di sanità pubblica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy. , (Italy)
  • 4 Unità di Medicina Interna e del Trapianto di Fegato, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy. , (Italy)
  • 5 Dipartimento di Scienze della vita e sanità pubblica, Università Cattolica del S. Cuore, Roma, Italy. , (Italy)
  • 6 Unità di Medicina Interna e del Trapianto di Fegato, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del S. Cuore, Roma, Italy. , (Italy)
  • 7 Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del S. Cuore, Roma, Italy; UOSD Malattie Emorragiche e Trombotiche, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy. Electronic address: [email protected] , (Italy)
Type
Published Article
Journal
Translational research : the journal of laboratory and clinical medicine
Publication Date
May 01, 2021
Volume
231
Pages
24–38
Identifiers
DOI: 10.1016/j.trsl.2020.11.003
PMID: 33171266
Source
Medline
Language
English
License
Unknown

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and ranges from simple steatosis to nonalcoholic steatohepatitis. Recently, a platelet role in NAFLD pathogenesis and progression has been reported in mouse models and in patients. We investigated whether platelets are involved in liver and systemic inflammation processes in NAFLD. In this exploratory study we recruited 24 consecutive patients with biopsy-proven diagnosis of NAFLD and 17 healthy volunteers. We measured plasma levels of inflammatory markers by ELISA. We investigated hemostatic and inflammatory transcripts in circulating platelets and leukocytes from NAFLD patients. We analyzed platelet and neutrophil extracellular traps (NET) accumulations in liver sinusoids using CD42 and H3 citrullinated histones immunohistochemical staining on liver biopsies. NAFLD patients had increased inflammation markers and lipolysaccharides plasma levels. We found significant increase of inflammatory transcripts in circulating platelets and not in leukocytes of NAFLD subjects compared with healthy controls. We demonstrated increased intrahepatic platelet accumulation that correlated with NAFLD activity score (NAS) score and intrahepatic neutrophil extracellular traps (NET) formation in liver biopsies of NAFLD patients. NET formation was higher in livers with higher NAS and inflammation scores. The presence of low-grade systemic inflammation and proinflammatory changes of circulating platelets indicate that platelets participate on systemic inflammatory changes associated with NAFLD. Liver platelet accumulation and liver NET formation, together with low-grade endotoxemia, suggest that platelets may act to protect the liver from invading microorganisms by favoring local NET formation. Copyright © 2020 Elsevier Inc. All rights reserved.

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