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Identification of patients at risk for NASH with significant fibrosis is therefore important. Although the established fibrosis score FIB\u20104 is suitable to exclude advanced fibrosis, it does not allow the prediction of significant fibrosis in NAFLD patients. We therefore evaluated whether the hepatokine fibroblast growth factor 21 (FGF21), a regulator of glucose and lipid metabolism, might identify \u2018at\u2010risk NASH\u2019 in NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>FGF21 levels were assessed by enzyme\u2010linked immunosorbent assay in sera from an exploration (<jats:italic>n<\/jats:italic>\u2009=\u2009137) and a validation (<jats:italic>n<\/jats:italic>\u2009=\u200988) cohort of biopsy\u2010proven NAFLD patients with different disease activity and fibrosis stages. In addition, we evaluated whether the use of FGF21 could improve risk stratification in NAFLD patients with low (&lt;1.3) or intermediate (1.3\u20132.67) FIB\u20104.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FGF21 levels could significantly discriminate between NASH and non\u2010alcoholic fatty liver (NAFL) patients, even in the absence of diabetes. Moreover, patients with NASH and fibrosis \u2265F2 showed significantly higher FGF21 levels compared to NAFLD patients without significant fibrosis. Significantly elevated FGF21 levels could even be detected in NAFLD patients with NASH and significant fibrosis despite low or intermediate FIB\u20104.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Serological FGF21 detection might allow the identification of NAFLD patients at risk and improves patient stratification in combination with FIB\u20104.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15686","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T11:49:49Z","timestamp":1691063389000},"page":"2668-2679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hepatokine\u2010based identification of fibrotic <scp>NASH<\/scp> and improved risk stratification in a multicentre cohort of <scp>NAFLD<\/scp> patients"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6889-2955","authenticated-orcid":false,"given":"Martin","family":"Franck","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"John","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherin","family":"Al\u00a0Aoua","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology Hannover Medical School  Hannover 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