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Lysosomal acid lipase (LAL), a central enzyme in intracellular lipid hydrolysis, has been reported to be reduced in MASLD and linked to liver injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To evaluate whether baseline LAL activity predicts long-term progression of MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively followed up 144 adults with biopsy-proven MASLD for a minimum of 5\u00a0years (median 8.1). All patients underwent a FibroScan\u00ae at baseline and follow-up and 94 of them also had paired liver biopsies. LAL activity (expressed as LAL\/platelet-LAL\/ptls) was measured on dried blood spots. Liver disease progression was defined by meeting of the histological endpoint at follow-up (i.e., development of MASH and\/or NAS worsening\u2009\u2265\u20091 point and\/or fibrosis progression\u2009\u2265\u20091 stage) or by liver stiffness measurement (LSM) worsening at Fibroscan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 94 biopsied patients, 26% met the composite histological endpoint and had significantly lower baseline LAL\/ptls ratio, higher HOMA-IR, CAP and LSM. In particular, lower LAL\/ptls was strongly related to the worsening of inflammation. In multivariate analysis, lower ln-transformed LAL\/ptls ratio independently predicted histological progression (OR 0.51, 95% CI 0.04\u20130.60,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.018). No association emerged between baseline LAL\/ptls ratio and non-invasive progression by FibroScan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lower LAL\/ptls ratio identifies MASLD patients at increased risk of histological progression and complements non-invasive tools by reflecting biological pathways linked to inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                    <jats:p>Progression of MASLD and levels of Lysosomal acid lipase activity<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12072-026-11084-6","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T14:36:32Z","timestamp":1776868592000},"page":"1073-1083","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low lysosomal acid lipase activity is associated with histological progression of metabolic dysfunction-associated steatotic liver disease"],"prefix":"10.1007","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6958-927X","authenticated-orcid":false,"given":"Rosa","family":"Lombardi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Cinque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Cespiati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bertelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Pisano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Oberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Fatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaqueline","family":"Curr\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Calzavara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Alletto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Garavaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Cincotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Ludovica","family":"Fracanzani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Gomaraschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"issue":"5","key":"11084_CR1","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1053\/j.gastro.2025.02.044","volume":"169","author":"ZM Younossi","year":"2025","unstructured":"Younossi ZM, Zelber-Sagi S, Lazarus JV, Wong VW, Yilmaz Y, Duseja A, et al. 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All other authors declare no financial interests.","order":1,"name":"Ethics","label":"Conflict of interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol was approved by the Institutional Review Board of Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico of Milan (12\/05\/2022\u20130025162-U). For all patients, informed consent to use clinical, histological and laboratory data was obtained across decades, according to the ethical guidelines of the 1975 Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}