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We aimed to investigate the link between histological myofibroblast activation (alpha-smooth-muscle-actin: \u03b1SMA) and sinusoidal capillarization (CD34) markers to PH severity in patients with chronic liver disease (CLD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with CLD underwent hepatic venous pressure gradient (HVPG) measurement and liver biopsy. Liver samples were stained by picrosirius-red for collagen proportionate area (CPA) and for \u03b1SMA\/CD34. Quantitative histomorphometry was performed on full-slide scans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>102 patients (63.7% male, median age 56.4\u00a0years, mainly steatotic liver disease: 58.8%) were included. The median HVPG was 13 [10\u201318] mmHg and severe PH (HVPG\u2009\u2265\u200916\u00a0mmHg, PH16) was found in 35.3%. Median liver-stiffness was 30.6 [19.1\u201357.6] kPa. In PH16 patients, fibrosis (CPA: 28.39 vs 17.72%), myofibroblast activation (\u03b1SMA: 10.84 vs 3.75%), and capillarization (CD34: 5.45 vs 2.67%) were significantly more pronounced (all p\u2009&lt;\u20090.001 vs. no PH16). CD34 showed a higher correlation to HVPG (rho\u2009=\u20090.505) than CPA (rho\u2009=\u20090.472) and \u03b1SMA (rho\u2009=\u20090.347, all p\u2009&lt;\u20090.001). CD34 expression was independently correlated with enhanced liver fibrosis (ELF) test and von Willebrand factor (VWF). When partially adjusting for fibrosis severity, patients with less severe fibrosis and high \u03b1SMA or CD34 had a trend for higher HVPG, whereas in intermediate fibrosis, only CD34-high patients trended higher HVPG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CPA, CD34 and \u03b1SMA expression all correlate with PH severity. CD34 represents a histologic sinusoidal capillarization marker that correlates with circulating VWF and ELF. \u03b1SMA and CD34 represent potential histologic markers of PH beyond the static component.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12072-026-11133-0","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:53:00Z","timestamp":1785171180000},"page":"1432-1445","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Histomorphometry indicates distinct contributions of myofibroblast activation and sinusoidal capillarization to portal hypertension"],"prefix":"10.1007","volume":"20","author":[{"given":"Thomas","family":"Sorz-Nechay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt S.","family":"Hofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"K\u00f6nigshofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Treitler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Semmler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Simbrunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad","family":"Taru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Bonitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriette","family":"Horstmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Kramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Zinober","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Regnat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Neudert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Kaltenecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behrang","family":"Mozayani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"Kain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Mandorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Schwabl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4590-3583","authenticated-orcid":false,"given":"Thomas","family":"Reiberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"2","key":"11133_CR1","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","volume":"79","author":"H Devarbhavi","year":"2023","unstructured":"Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. 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GS received travel support from Amgen. BS received travel support from AbbVie, Gilead and Falk. MM received grant support from Echosens, served as a speaker and\/or consultant and\/or advisory board member for AbbVie, AstraZeneca, Collective Acumen, Echosens, Gilead, Ipsen, Takeda, and W. L. Gore & Associates, and received travel support from AbbVie and Gilead. BM received a speaker fee from Astellas Pharma and Springer Medicine. MT received grant support from Albireo, Alnylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda and UltraGenyx; honoraria for consulting from AbbVie, Albireo, Boehringer Ingelheim, BiomX, Falk, Genfit, Gilead, Hightide, Intercept, Jannsen, MSD, Novartis, Phenex, Pliant, Regulus, Siemens and Shire; speaker fees from Albireo, Bristol-Myers Squibb, Falk, Gilead, Intercept, MSD and Madrigal; and travel support from AbbVie, Falk, Gilead and Intercept. PS received consulting fees from PharmaIN and payment for manuscript writing from the Falk Foundation. TR received grant support from Abbvie, Boehringer Ingelheim, Gilead, Intercept\/Advanz Pharma, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, Siemens and W. L. Gore & Associates; speaking honoraria from Abbvie, Gilead, \/Advanz Pharma, Roche, MSD, W. L. Gore & Associates; consulting\/advisory board fee from Abbvie, Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Intercept\/Advanz Pharma, MSD, Resolution Therapeutics, Siemens; and travel support from Abbvie, Boehringer Ingelheim, Dr. Falk Pharma, Gilead and Roche. TSN, PK, AT, VT, KB, HH, GK, KZ, KR, BN, CCK and RK declare no conflicts of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted within the frameworks of the prospective Vienna Cirrhosis Study (clinicaltrials.gov number: NCT03267615), which was ethically approved by the local ethics committee of the Medical University of Vienna (ethics number: 1262\/2017).","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study involved human participants and was performed in accordance with the Declaration of Helsinki, in addition to institutional and national research committee ethical standards.","order":3,"name":"Ethics","label":"Statement of human and animal rights","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients signed an informed consent form for participation in the prospective Vienna Cirrhosis Study (clinicaltrials.gov number: NCT03267615).","order":4,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}}]}}