{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:13:14Z","timestamp":1788865994104,"version":"build-2803163510"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":82,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP26fk0210210"],"award-info":[{"award-number":["JP26fk0210210"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25fk0310540"],"award-info":[{"award-number":["JP25fk0310540"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-58113-w","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T18:22:19Z","timestamp":1781806939000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CLEIA-based type IV collagen 7S for second-step assessment of MRE-defined clinically significant fibrosis in MASLD with indeterminate FIB-4"],"prefix":"10.1038","volume":"16","author":[{"given":"Shiho","family":"Murakami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miwa","family":"Kawanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kento","family":"Imajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syohei","family":"Shiota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Sue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuto","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Onishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinobu","family":"Takaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyo","family":"Urata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Kawamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyuki","family":"Otsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"58113_CR1","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","volume":"77","author":"ZM Younossi","year":"2023","unstructured":"Younossi, Z. M. et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology 77, 1335\u20131347 (2023).","journal-title":"Hepatology"},{"key":"58113_CR2","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.jhep.2018.05.036","volume":"69","author":"C Estes","year":"2018","unstructured":"Estes, C. et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016\u20132030. J. Hepatol. 69, 896\u2013904 (2018).","journal-title":"J. Hepatol."},{"key":"58113_CR3","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.cgh.2022.01.002","volume":"21","author":"H Fujii","year":"2023","unstructured":"Fujii, H. et al. Clinical outcomes in biopsy-proven nonalcoholic fatty liver disease patients: a multicenter registry-based cohort study. Clin. Gastroenterol. Hepatol. 21, 370\u2013379 (2023).","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"6","key":"58113_CR4","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1053\/j.gastro.2020.01.043","volume":"158","author":"RS Taylor","year":"2020","unstructured":"Taylor, R. S. et al. Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis. Gastroenterology. 158, 1611-1625.e12 (2020).","journal-title":"Gastroenterology"},{"key":"58113_CR5","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1097\/HEP.0000000000000323","volume":"77","author":"ME Rinella","year":"2023","unstructured":"Rinella, M. E. et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 77, 1797\u20131835 (2023).","journal-title":"Hepatology"},{"key":"58113_CR6","doi-asserted-by":"crossref","unstructured":"EASL-EASD-EASO Clinical Practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). Obes Facts 17 ,374-444 (2024).","DOI":"10.1159\/000539371"},{"key":"58113_CR7","doi-asserted-by":"crossref","unstructured":"Bansal, M. B. et al. Semaglutide therapy for metabolic dysfunction-associated steatohepatitis: november 2025 updates to AASLD practice guidance. Hepatology\u00a083, 1326-1340 (2026)","DOI":"10.1097\/HEP.0000000000001608"},{"key":"58113_CR8","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1056\/NEJMoa2309000","volume":"390","author":"SA Harrison","year":"2024","unstructured":"Harrison, S. A. et al. A Phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 390, 497\u2013509 (2024).","journal-title":"N Engl J Med."},{"key":"58113_CR9","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/j.cgh.2009.05.033","volume":"7","author":"AG Shah","year":"2009","unstructured":"Shah, A. G. et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 7, 1104\u20131112 (2009).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"58113_CR10","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/hep.21178","volume":"43","author":"RK Sterling","year":"2006","unstructured":"Sterling, R. K. et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection. Hepatology 43, 1317\u20131325 (2006).","journal-title":"Hepatology"},{"key":"58113_CR11","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.jhep.2019.03.033","volume":"71","author":"A Srivastava","year":"2019","unstructured":"Srivastava, A. et al. Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease. J. Hepatol. 71, 371\u2013378 (2019).","journal-title":"J. Hepatol."},{"key":"58113_CR12","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.jhep.2023.04.025","volume":"79","author":"JX Liang","year":"2023","unstructured":"Liang, J. X. et al. An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography. J. Hepatol. 79, 592\u2013604 (2023).","journal-title":"J. Hepatol."},{"key":"58113_CR13","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1053\/j.gastro.2015.11.048","volume":"150","author":"K Imajo","year":"2016","unstructured":"Imajo, K. et al. Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than Transient Elastography. Gastroenterology 150, 626-637.e7 (2016).","journal-title":"Gastroenterology"},{"key":"58113_CR14","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1053\/j.gastro.2008.03.076","volume":"135","author":"L Huwart","year":"2008","unstructured":"Huwart, L. et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology 135, 32\u201340 (2008).","journal-title":"Gastroenterology"},{"key":"58113_CR15","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1053\/j.gastro.2004.08.052","volume":"127","author":"WM Rosenberg","year":"2004","unstructured":"Rosenberg, W. M. et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology 127, 1704\u20131713 (2004).","journal-title":"Gastroenterology"},{"key":"58113_CR16","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1111\/hepr.13495","volume":"50","author":"C Inadomi","year":"2020","unstructured":"Inadomi, C. et al. Accuracy of the enhanced liver fibrosis test, and combination of the enhanced liver fibrosis and non-invasive tests for the diagnosis of advanced liver fibrosis in patients with non-alcoholic fatty liver disease. Hepatol. Res. 50, 682\u2013692 (2020).","journal-title":"Hepatol. Res."},{"key":"58113_CR17","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.23923","volume":"4","author":"ZM Younossi","year":"2021","unstructured":"Younossi, Z. M. et al. Performance of the enhanced liver fibrosis test to estimate advanced fibrosis among patients with nonalcoholic fatty liver disease. JAMA Netw. Open 4, e2123923 (2021).","journal-title":"JAMA Netw. Open"},{"key":"58113_CR18","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s00535-022-01932-1","volume":"58","author":"Y Kamada","year":"2023","unstructured":"Kamada, Y. et al. SWOT analysis of noninvasive tests for diagnosing NAFLD with severe fibrosis: an expert review by the JANIT Forum. J Gastroenterol. 58, 79\u201397 (2023).","journal-title":"J Gastroenterol."},{"key":"58113_CR19","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1093\/clinchem\/37.9.1639","volume":"37","author":"I Nishizono","year":"1991","unstructured":"Nishizono, I. et al. Rapid and sensitive chemiluminescent enzyme immunoassay for measuring tumor markers. Clin. Chem. 37, 1639\u20131644 (1991).","journal-title":"Clin. Chem."},{"key":"58113_CR20","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000563","volume":"9","author":"H Ishiba","year":"2025","unstructured":"Ishiba, H. et al. Accuracy of type IV collagen 7S versus enhanced liver fibrosis score for diagnosing fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. Hepatol. Commun. 9, e0563 (2025).","journal-title":"Hepatol. Commun."},{"key":"58113_CR21","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1002\/hep.1840200403","volume":"20","author":"Y Murawaki","year":"1994","unstructured":"Murawaki, Y. et al. Serum type III procollagen peptide, type IV collagen 7S domain, central triple-helix of type IV collagen and tissue inhibitor of metalloproteinases in patients with chronic viral liver disease: relationship to liver histology. Hepatology 20, 780\u2013787 (1994).","journal-title":"Hepatology"},{"key":"58113_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2025.100668","volume":"4","author":"H Ishiba","year":"2025","unstructured":"Ishiba, H. et al. Prediction of advanced fibrosis in metabolic dysfunction-associated steatotic liver disease by Type IV collagen 7S. Gastro. Hep. Adv. 4, 100668 (2025).","journal-title":"Gastro. Hep. Adv."},{"key":"58113_CR23","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1111\/hepr.13857","volume":"53","author":"Y Honda","year":"2023","unstructured":"Honda, Y. et al. Meta-analysis of the diagnostic accuracy of serum type IV collagen 7S concentration for the staging of liver fibrosis in nonalcoholic fatty liver disease. Hepatol. Res. 53, 219\u201327 (2023).","journal-title":"Hepatol. Res."},{"key":"58113_CR24","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s00535-007-2014-3","volume":"42","author":"M Yoneda","year":"2007","unstructured":"Yoneda, M. et al. Type IV collagen 7s domain is an independent clinical marker of the severity of fibrosis in patients with nonalcoholic steatohepatitis before the cirrhotic stage. J. Gastroenterol. 42, 375\u2013381 (2007).","journal-title":"J. Gastroenterol."},{"key":"58113_CR25","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1111\/hepr.14202","volume":"55","author":"M Kawanaka","year":"2025","unstructured":"Kawanaka, M. et al. The new assay type IV collagen 7S (CLEIA) is a useful test to identify progressive fibrosis in chronic liver disease: a study based on magnetic resonance elastography. Hepatol .Res. 55, 994\u20131004 (2025).","journal-title":"Hepatol .Res."},{"key":"58113_CR26","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1111\/hepr.13605","volume":"51","author":"T Shima","year":"2021","unstructured":"Shima, T. et al. A novel rapid immunoassay of serum type IV collagen 7S for the diagnosis of fibrosis stage of nonalcoholic fatty liver diseases. Hepatol. Res. 51, 263\u2013276 (2021).","journal-title":"Hepatol. Res."},{"key":"58113_CR27","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1002\/prca.201300010","volume":"7","author":"A Kuno","year":"2013","unstructured":"Kuno, A. et al. Reconstruction of a robust glycodiagnostic agent supported by multiple lectin-assisted glycan profiling. Proteom. Clin. Appl. 7, 642\u2013647 (2013).","journal-title":"Proteom. Clin. Appl."},{"key":"58113_CR28","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1007\/s00535-014-0946-y","volume":"50","author":"T Toshima","year":"2015","unstructured":"Toshima, T. et al. A novel serum marker, glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP), for assessing liver fibrosis. J. Gastroenterol. 50, 76\u201384 (2015).","journal-title":"J. Gastroenterol."},{"key":"58113_CR29","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1007\/s00535-017-1425-z","volume":"53","author":"K Shirabe","year":"2018","unstructured":"Shirabe, K. et al. Mac-2 binding protein glycan isomer (M2BPGi) is a new serum biomarker for assessing liver fibrosis: more than a biomarker of liver fibrosis. J. Gastroenterol. 53, 819\u2013826 (2018).","journal-title":"J. Gastroenterol."},{"key":"58113_CR30","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1093\/aje\/kwac218","volume":"192","author":"NA Obuchowski","year":"2023","unstructured":"Obuchowski, N. A. Comparing the accuracy of diagnostic tests when disease is characterized by an ordinal scale. Am. J. Epidemiol. 192, 632\u2013643 (2023).","journal-title":"Am. J. Epidemiol."},{"key":"58113_CR31","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1016\/j.acra.2005.05.013","volume":"12","author":"NA Obuchowski","year":"2005","unstructured":"Obuchowski, N. A. Estimating and comparing diagnostic tests\u2019 accuracy when the gold standard is not binary. Acad. Radiol. 12, 1198\u20131204 (2005).","journal-title":"Acad. Radiol."},{"key":"58113_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2023.101133","volume":"29","author":"ME Rinella","year":"2024","unstructured":"Rinella, M. E. et al. A multisociety delphi consensus statement on new fatty liver disease nomenclature. Ann. Hepatol. 29, 101133 (2024).","journal-title":"Ann. Hepatol."},{"key":"58113_CR33","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1080\/10543406.2019.1632876","volume":"30","author":"J Hua","year":"2020","unstructured":"Hua, J. et al. A comprehensive and comparative review of optimal cut-points selection methods for diseases with multiple ordinal stages. J. Biopharm. Stat. 30, 46\u201368 (2020).","journal-title":"J. Biopharm. Stat."},{"key":"58113_CR34","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1053\/j.gastro.2005.03.084","volume":"128","author":"V Ratziu","year":"2005","unstructured":"Ratziu, V. et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 128, 1898\u20131906 (2005).","journal-title":"Gastroenterology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-58113-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-58113-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-58113-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:04:06Z","timestamp":1788865446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-58113-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["58113"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-58113-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]},"assertion":[{"value":"6 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Miwa Kawanaka has received consulting fees from Fujirebio, AbbVie Inc, and Souwakai. Akinobu Takaki has received consulting fees from Souwakai. All other authors declare no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"28003"}}