{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T16:00:28Z","timestamp":1776873628925,"version":"3.51.2"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","award":["CPDA110795"],"award-info":[{"award-number":["CPDA110795"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>SerpinB3 is a cysteine protease inhibitor involved in liver disease progression due to its proinflammatory and profibrogenic properties. The polymorphic variant SerpinB3\u2010PD (SB3\u2010PD), presents a substitution in its reactive centre loop, determining the gain of function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To disclose the clinical characteristics of a cohort of patients with cirrhosis in relation to the presence of SB3\u2010PD and to assess the effect of this genetic variant on fibrogenic and inflammatory cytokines in\u00a0vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed SB3 polymorphism in 90 patients with cirrhosis, prospectively followed up in our referral centre. We used HepG2 and HuH\u20107 cells transfected to overexpress either wild\u2010type SB3 (SB3\u2010WT) or SB3\u2010PD to assess their endogenous effect, while LX2 and THP\u20101 cells were treated with exogenous SB3\u2010WT or SB3\u2010PD proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients carrying SB3\u2010PD had more severe portal hypertension and higher MELD scores, than patients carrying SB3\u2010WT. In multivariate analysis, SB3\u2010PD was an independent predictor of cirrhosis complications. Patients with SB3\u2010PD polymorphism presented with more severe liver fibrosis and inflammatory features. Hepatoma cells overexpressing SB3\u2010PD showed higher TGF\u2010\u03b21 expression than controls. The addition of recombinant SB3\u2010PD induced an up\u2010regulation of TGF\u2010\u03b21 in LX2 cells and a more prominent inflammatory profile in THP\u20101 cells, compared to the effect of SB3\u2010WT protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The polymorphic variant SB3\u2010PD is highly effective in determining activation of TGF\u2010\u03b21 and inflammation in\u00a0vitro. Patients with cirrhosis who carry SB3\u2010PD polymorphism may be more prone to develop severe liver disease progression. However, further validation studies are warranted to support the <jats:italic>in\u00a0vivo<\/jats:italic> relevance of this polymorphism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17804","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T23:45:08Z","timestamp":1700783108000},"page":"380-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The polymorphic variant of SerpinB3 (SerpinB3\u2010PD) is associated with faster cirrhosis decompensation"],"prefix":"10.1111","volume":"59","author":[{"given":"Andrea","family":"Martini","sequence":"first","affiliation":[{"name":"Unit of Internal Medicine and Hepatology, Department of Medicine Azienda Ospedaliera\u2010Universit\u00e0  Padova Italy"},{"name":"European Reference Network \u2013 ERN RARE\u2010LIVER, Department of Medicine Azienda Ospedaliera\u2010Universit\u00e0  Padova 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