{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:07:45Z","timestamp":1792080465037,"version":"4.4.0"},"reference-count":124,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T00:00:00Z","timestamp":1613260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The prevalence of obesity or metabolic syndrome is increasing worldwide (globally metabodemic). Approximately 25% of the adult general population is suffering from nonalcoholic fatty liver disease (NAFLD), which has become a serious health problem. In 2020, global experts suggested that the nomenclature of NAFLD should be updated to metabolic-dysfunction-associated fatty liver disease (MAFLD). Hepatic fibrosis is the most significant determinant of all cause- and liver -related mortality in MAFLD. The non-invasive test (NIT) is urgently required to evaluate hepatic fibrosis in MAFLD. The fibrosis-4 (FIB-4) index is the first triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness, especially for general physicians or endocrinologists, although the FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration-controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the second step after triaging by the FIB-4 index. The leading cause of mortality in MAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. MAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation. The FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocellular carcinoma, but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, the FIB-4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of the FIB-4 index in the management of MAFLD.<\/jats:p>","DOI":"10.3390\/life11020143","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T08:53:56Z","timestamp":1613292836000},"page":"143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4342-1361","authenticated-orcid":false,"given":"Yoshio","family":"Sumida","sequence":"first","affiliation":[{"name":"Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutoshi","family":"Tokushige","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women\u2019s Medical University, Tokyo 162-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miwa","family":"Kawanaka","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine2, Kawasaki Medical School, Okayama 700-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1267-9623","authenticated-orcid":false,"given":"Hideki","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 558-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1267-9623","authenticated-orcid":false,"given":"Masato","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1931-6326","authenticated-orcid":false,"given":"Kento","family":"Imajo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-1436","authenticated-orcid":false,"given":"Hirokazu","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 840-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Loco Medical General Institute, Saga 840-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ono","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Women\u2019s Medical University Medical Center East, Tokyo 116-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Nozaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Hyogo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, JA Hiroshima General Hospital, Hiroshima 738-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Koseki","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka 564-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7064-4325","authenticated-orcid":false,"given":"Takumi","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-902X","authenticated-orcid":false,"given":"Yoshihiro","family":"Kamada","sequence":"additional","affiliation":[{"name":"Department of Advanced Gastroenterology &amp; Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-902X","authenticated-orcid":false,"given":"Takeshi","family":"Okanoue","sequence":"additional","affiliation":[{"name":"Hepatology Center, Saiseikai Suita Hospital, Osaka 564-0013, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-1436","authenticated-orcid":false,"given":"Atsushi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Japan Study Group of NAFLD (JSG-NAFLD)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"GBD 2015 Obesity Collaborators, Afshin, A., Forouzanfar, M.H., Reitsma, M.B., Sur, P., Estep, K., Lee, A., Marczak, L., Mokdad, A.H., and Moradi-Lakeh, M. 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