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The current gold standard for liver fibrosis is invasive liver biopsy. Therefore, a less invasive biomarker that accurately reflects the stage of liver fibrosis is highly desirable.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This study enrolled 269 patients with liver biopsy-proven MASLD. Patients were divided into three groups (F0\/1 (<jats:italic>n<\/jats:italic>\u2009=\u200941\/85), F2 (<jats:italic>n<\/jats:italic>\u2009=\u200947), and F3\/4 (<jats:italic>n<\/jats:italic>\u2009=\u200972\/24)) according to fibrosis stage. We performed serum <jats:italic>N<\/jats:italic>-glycomics and identified glycan biomarker for fibrosis stage. Moreover, we explored the carrier proteins and developed a sandwich ELISA to measure <jats:italic>N<\/jats:italic>-glycosylation changes of carrier protein.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Comprehensive <jats:italic>N<\/jats:italic>-glycomic analysis revealed significant changes in the expression of A2F bisect and its precursors as fibrosis progressed. The sum of neutral <jats:italic>N<\/jats:italic>-glycans carrying bisecting GlcNAc and core Fuc (neutral sum) had a better diagnostic performance to evaluate advanced liver fibrosis (AUC\u2009=\u20090.804) than conventional parameters (FIB4 index, aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), and serum level of Mac-2-binding protein glycol isomer\u00a0(M2BPGi). The combination of the neutral sum and FIB4 index enhanced diagnostic performance (AUC\u2009=\u20090.840). IgM, IgA, and complement C3 were identified as carrier proteins with A2F bisect <jats:italic>N<\/jats:italic>-glycan. A sandwich ELISA based on <jats:italic>N<\/jats:italic>-glycans carrying bisecting GlcNAc and IgA showed similar diagnostic performance than the neutral sum.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>A2F bisect <jats:italic>N<\/jats:italic>-glycan and its precursors are promising candidate biomarkers for advanced fibrosis in MASLD patients. Analysis of these glycan alterations on IgA may have the potential to serve as a novel ELISA diagnostic tool for MASLD in routine clinical practice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical trial number<\/jats:title>\n            <jats:p>UMIN000030720.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00535-024-02206-8","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T02:03:08Z","timestamp":1737684188000},"page":"456-468","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Elevated A2F bisect N-glycans of serum IgA reflect progression of liver fibrosis in patients with MASLD"],"prefix":"10.1007","volume":"60","author":[{"given":"Hisatoshi","family":"Hanamatsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goki","family":"Suda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatsugu","family":"Ohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuharu","family":"Tamaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Hikita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Haga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Maekawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhiko","family":"Kakisaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Nakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Sho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuaki","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Kurosaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Asahina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinobu","family":"Taketomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Ueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Takehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nishikaze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichi","family":"Furukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"2206_CR1","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1097\/hep.0000000000000004","volume":"77","author":"ZM Younossi","year":"2023","unstructured":"Younossi ZM, Golabi P, Paik JM, et al. 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