{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:15:37Z","timestamp":1787015737838,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T00:00:00Z","timestamp":1682208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      Programmed cell death 1\/programmed cell death\u2010ligand 1 (PD\u20101\/PDL\u20101) axis has been reported to modulate liver inflammation and progression to hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Here, we examined whether the\n                      <jats:italic>PDCD1<\/jats:italic>\n                      variation is associated with NAFLD severity in individuals with liver biopsy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined the impact of\n                      <jats:italic>PDCD1<\/jats:italic>\n                      gene variants on HCC, as robust severe liver disease phenotype in UK Biobank participants. The strongest genetic association with the rs13023138 G&gt;C variation was subsequently tested for association with liver damage in 2889 individuals who underwent liver biopsy for suspected nonalcoholic steatohepatitis (NASH). Hepatic transcriptome was examined by RNA\u2010Seq in a subset of NAFLD individuals (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009121). Transcriptomic and deconvolution analyses were performed to identify biological pathways modulated by the risk allele.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The rs13023138 C&gt;G showed the most robust association with HCC in UK Biobank (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20095.28E\u20104, OR\u2009=\u20091.32, 95% CI [1.1, 1.5]). In the liver biopsy cohort,\n                      <jats:italic>rs13023138<\/jats:italic>\n                      G allele was independently associated with severe steatosis (OR 1.17, 95% CI 1.02\u20101.34;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.01), NASH (OR 1.22, 95% CI 1.09\u20101.37;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001) and advanced fibrosis (OR 1.26, 95% CI 1.06\u20101.50;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.007). At deconvolution analysis, rs13023138 G&gt;C allele was linked to higher hepatic representation of M1 macrophages, paralleled by upregulation of pathways related to inflammation and higher expression of CXCR6.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>PDCD1 rs13023138<\/jats:italic>\n                      G allele was associated with HCC development in the general population and with liver disease severity in patients at high risk of NASH.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15586","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T01:33:05Z","timestamp":1682299985000},"page":"1761-1771","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Programmed cell death 1 genetic variant and liver damage in nonalcoholic fatty liver disease"],"prefix":"10.1111","volume":"43","author":[{"given":"Rosaria M.","family":"Pipitone","sequence":"first","affiliation":[{"name":"Sezione di Gastroenterologia e Epatologia, Dipartimento di Promozione della Salute, Materno\u2010Infantile, di Medicina Interna e Specialistica di Eccellenza \u201cG. D'Alessandro\u201d University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Malvestiti","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9518-4751","authenticated-orcid":false,"given":"Grazia","family":"Pennisi","sequence":"additional","affiliation":[{"name":"Sezione di Gastroenterologia e Epatologia, Dipartimento di Promozione della Salute, Materno\u2010Infantile, di Medicina Interna e Specialistica di Eccellenza \u201cG. 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