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    Poster Networking

    Immunothrombosis

    Poster Networking Session

    PB0802 - Platelet features that identify early stages of liver disease progression.

    Monday, June 26, 2023
    18:30 – 19:30 ET
    Room: Exhibition
    Background: Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent and costly manifestation of the metabolic syndrome with high morbidity and mortality rates. Platelets have been implicated in the progression of chronic liver disease from simple hepatic steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and cirrhosis. Patients with cirrhosis have a lower platelet count and a heightened risk of thrombosis. However, the functional state of circulating platelets at various stages of liver disease is debated and poorly understood.

    Aims: To identify phenotypical and functional platelet features that characterise the early stages of liver disease and may promote the amplification of the inflammatory state that drives disease progression.

    Methods: Patients with histologically proven NAFLD (n=14 NAFL, n=20 NASH) were enrolled according to EASL-EASD-EASO guidelines. Citrated venous whole blood was processed within 1 hour from withdrawal to characterise the phenotype, function, and immune interactions of platelets by multiparameter flow cytometry. The study was approved by the Ethics Committee of the Hospital Umberto I (Rome, Italy). All participants gave written informed consent.

    Results: Liver disease severity correlated with an increase of platelet size and of the immature platelet fraction, suggesting an increase in platelet turnover, even though only 20% of participants had platelet count below the normal range.
    Compared to NAFL, circulating platelets of NASH patients expressed higher levels of receptors implicated in immune-like functions (CD62P, CD42b, TLR4, CLEC2, CD44 and MHC-I) and exhibited a higher platelet responsiveness to agonists of Immunoreceptor Tyrosine-based Activation Motif-coupled receptors.
    NAFL, but not NASH patients, exhibited higher levels of platelet aggregates with CD8+T-cells and NKT-cells in peripheral blood, possibly because in more advanced stages of the disease these aggregates relocate to the liver.

    Conclusion(s): The study identified platelet pro-inflammatory features that characterise early stages of chronic liver disease with utility for its non-invasive diagnosis or as novel molecular targets for its treatment.