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There has been reported an inverse correlation between PLTs and progressive MASLD, which is also affected by the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 C&gt;G mutation. However, the correlation between low PLTs and PNPLA3 genotype has been poorly investigated. We stratified 1155 biopsy-proven MASLD patients according to PNPLA3 genotype. The hepatic expression of genes involved in megakaryopoiesis was investigated in n = 167 bariatric patients by RNAseq. PLT count progressively decreased according to the number of PNPLA3 at-risk alleles, irrespective of the presence of advanced fibrosis. The hepatic expression of genes involved in PLT biogenesis was associated with the PNPLA3 GG genotype. Finally, the presence of the PNPLA3 homozygosity flattened the accuracy of fibrosis-4 (FIB-4) in discriminating histological fibrosis stages. The PNPLA3 GG genotype may underpower the accuracy of NITs which include PLT count in identifying those patients with potentially reversible stages of fibrosis.<\/jats:p>","DOI":"10.3390\/ijms242015046","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T10:23:42Z","timestamp":1696933422000},"page":"15046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["PNPLA3 rs738409 Genetic Variant Inversely Correlates with Platelet Count, Thereby Affecting the Performance of Noninvasive Scores of Hepatic Fibrosis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4161-4178","authenticated-orcid":false,"given":"Marica","family":"Meroni","sequence":"first","affiliation":[{"name":"Medicine and Metabolic Diseases, Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4343-7213","authenticated-orcid":false,"given":"Paola","family":"Dongiovanni","sequence":"additional","affiliation":[{"name":"Medicine and Metabolic Diseases, Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.cgh.2023.04.015","article-title":"The Global Burden of Liver Disease","volume":"21","author":"Younossi","year":"2023","journal-title":"Clin. 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