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This study aimed to identify multiomics-based predictors of NAFLD progression, as assessed by changes in serial FibroScan-aspartate aminotransferase (FAST) scores during lifestyle modification. A total of 266 patients with available metabolomics and genotyping data were included. The follow-up sub-cohort included patients with paired laboratory and transient elastography results (n = 160). The baseline median FAST score was 0.37. The PNPLA3 rs738409 genotype was significantly associated with a FAST score &gt; 0.35. Circulating metabolomics significantly associated with a FAST score &gt; 0.35 included SM C24:0 (odds ratio [OR] = 0.642; 95% confidence interval [CI], 0.463\u20130.891), PC ae C40:6 (OR = 0.477; 95% CI, 0.340\u20130.669), lysoPC a C18:2 (OR = 0.570; 95% CI, 0.417\u20130.779), and tyrosine (OR = 2.743; 95% CI, 1.875\u20134.014). A combination of these metabolites and PNPLA3 genotype yielded a c-index = 0.948 for predicting a FAST score &gt; 0.35. In the follow-up sub-cohort (median follow-up = 23.7 months), 47\/76 patients (61.8%) with a baseline FAST score &gt; 0.35 had a follow-up FAST score \u2264 0.35. An improved FAST score at follow-up was significantly associated with age, serum alanine aminotransferase, and tyrosine. In conclusion, baseline risk stratification in NAFLD patients may be assisted using a multiomics-based model. Particularly, patients with increased tyrosine may benefit from an earlier switch to pharmacologic approaches.<\/jats:p>","DOI":"10.3390\/metabo13030444","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T04:05:23Z","timestamp":1679285123000},"page":"444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0723-1285","authenticated-orcid":false,"given":"Hwi Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2268-6029","authenticated-orcid":false,"given":"Da Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Metabolomics Core Facility, Department of Transdisciplinary Research and Collaboration, Biomedical Research Institute, Seoul National University Hospital, Seoul 03082, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4051-0350","authenticated-orcid":false,"given":"Hye Ah","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Ewha Womans University Medical Center, Seoul 07985, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-8273","authenticated-orcid":false,"given":"Joo-Youn","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea"},{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-1007","authenticated-orcid":false,"given":"Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine and Seoul Metropolitan Government Boramae Medical Center, Seoul 07061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.jhep.2019.06.021","article-title":"The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis","volume":"71","author":"Younossi","year":"2019","journal-title":"J. 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