• Transl Res · May 2021

    Nonalcoholic fatty liver disease (NAFLD) severity is associated to a non-hemostatic contribution and pro-inflammatory phenotype of platelets.

    • Luca Miele, Maria Adele Alberelli, Maurizio Martini, Antonio Liguori, Giuseppe Marrone, Alessandra Cocomazzi, Fabio Maria Vecchio, Raffaele Landolfi, Antonio Gasbarrini, Antonio Grieco, and Erica De Candia.
    • 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: luca.miele@policlinicogemelli.it.
    • Transl Res. 2021 May 1; 231: 24-38.

    AbstractNonalcoholic 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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