{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:40:38Z","timestamp":1792525238570,"version":"4.5.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":88,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Methotrexate is a first-line therapy for rheumatoid arthritis, psoriatic arthritis, and psoriasis, but its long-term use has been associated with hepatic fibrosis, highlighting the need for effective screening strategies. In this context, and considering the limitations of liver biopsy as well as the high cost and limited availability of elastography, the FIB-4 score has emerged as the most widely used noninvasive screening tool. This multicenter cross-sectional study evaluated patients followed at specialized Rheumatology and Dermatology centers to assess the accuracy of FIB-4 in predicting advanced hepatic fibrosis in patients with rheumatoid arthritis, psoriatic arthritis, and psoriasis undergoing chronic methotrexate therapy. The specific objectives were to identify optimal cutoff values for FIB-4 in this population and factors associated with advanced fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Medical records, interviews, and physical examinations were used to collect demographic, clinical, laboratory, lifestyle, and treatment data, calculate age-adjusted FIB-4 scores, and assess disease activity using validated indices. Liver fibrosis and steatosis were evaluated by vibration-controlled transient elastography, and FIB-4 performance for detecting advanced fibrosis was analysed using age-stratified Receiver Operating Characteristic curves and multivariable logistic regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 172 patients were included, predominantly women, with a mean age of 58 years; rheumatoid arthritis was the most common underlying disease. Advanced fibrosis was identified by elastography in 11%. FIB-4 values increased progressively with fibrosis stage, and Receiver Operating Characteristic curve analysis identified a cutoff of 1.62 \u2014 a threshold not previously reported for methotrexate-treated patients. This cutoff demonstrated better performance in individuals younger than 65 years (Area Under the Curve\u2009=\u20090.68\n                      <jats:italic>versus<\/jats:italic>\n                      0.64 in those aged 65 years or older) and showed particular utility for ruling out advanced fibrosis. In multivariable analysis, a high-risk FIB-4 category, obesity,\n                      <jats:italic>diabetes mellitus<\/jats:italic>\n                      , and advanced hepatic steatosis were independently associated with advanced fibrosis, whereas inflammatory disease activity and cumulative methotrexate dose were not.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FIB-4 is an accessible and potentially useful tool for ruling out advanced hepatic fibrosis in methotrexate-treated patients younger than 65 years, demonstrating reasonable performance in this population. Advanced fibrosis is primarily driven by metabolic factors rather than methotrexate exposure or inflammatory disease activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42358-026-00567-7","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:43:41Z","timestamp":1784868221000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic performance of FIB-4 in detecting advanced liver fibrosis in patients with rheumatoid arthritis, psoriatic arthritis and psoriasis using methotrexate"],"prefix":"10.1186","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0371-1313","authenticated-orcid":false,"given":"Fernanda Luiza Schumacher","family":"Furlan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0692-1068","authenticated-orcid":false,"given":"Patricia","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9573-9438","authenticated-orcid":false,"given":"Alcindo","family":"Pissaia Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-557X","authenticated-orcid":false,"given":"Claudia Alexandra Pontes","family":"Ivantes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0979-3604","authenticated-orcid":false,"given":"Marcia","family":"Olandoski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1020-7211","authenticated-orcid":false,"given":"Adriane Reichert","family":"Faria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9729-4791","authenticated-orcid":false,"given":"Adriano Reinaldo","family":"Timm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5893-4213","authenticated-orcid":false,"given":"Jhony Maciel de","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3325-3414","authenticated-orcid":false,"given":"Giuliano Camati","family":"Dourado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1921-6878","authenticated-orcid":false,"given":"Lana Bassi","family":"Ferdinando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-5497","authenticated-orcid":false,"given":"Rebeca Rebou\u00e7as","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0447-2991","authenticated-orcid":false,"given":"Beatriz Gallo","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9504-8570","authenticated-orcid":false,"given":"Raphaela Suzin Marini","family":"Munaretto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9730-6860","authenticated-orcid":false,"given":"Odery","family":"Ramos Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"issue":"2","key":"567_CR1","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41584-022-00883-4","volume":"19","author":"V Di Martino","year":"2023","unstructured":"Di Martino V, Alivernini S, Tolusso B, et al. Busting the myth of methotrexate chronic hepatotoxicity. Nat Rev Rheumatol. 2023;19(2):96\u2013110.","journal-title":"Nat Rev Rheumatol"},{"issue":"3","key":"567_CR2","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1111\/liv.15811","volume":"44","author":"C Wang","year":"2024","unstructured":"Wang C, Xu Y, Li Y, et al. Ferritinophagy-mediated ferroptosis facilitates methotrexate-induced hepatotoxicity by high-mobility group box 1 (HMGB1). Liver Int. 2024;44(3):691\u2013705.","journal-title":"Liver Int"},{"issue":"12","key":"567_CR3","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.4254\/wjh.v13.i12.1828","volume":"13","author":"S Mazza","year":"2021","unstructured":"Mazza S, Sorce A, Peyrin-Biroulet L, et al. Liver-side of inflammatory bowel diseases: hepatobiliary and drug-induced disorders. World J Hepatol. 2021;13(12):1828\u201349.","journal-title":"World J Hepatol"},{"issue":"4","key":"567_CR4","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s13555-020-00409-4","volume":"10","author":"DMW Balak","year":"2020","unstructured":"Balak DMW, Hajdarbegovic E, van Doorn MBA, et al. Long-term safety of oral systemic therapies for psoriasis: a comprehensive review of the literature. Dermatol Ther. 2020;10(4):589\u2013613.","journal-title":"Dermatol Ther"},{"issue":"6","key":"567_CR5","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1016\/j.jaad.2021.02.019","volume":"84","author":"JM Gelfand","year":"2021","unstructured":"Gelfand JM, Shin DB, Lewis JD, et al. Risk of liver disease in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis receiving methotrexate: a population-based study. J Am Acad Dermatol. 2021;84(6):1636\u201343.","journal-title":"J Am Acad Dermatol"},{"key":"567_CR6","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1097\/HEP.0000000000000323","volume":"77","author":"ME Rinella","year":"2023","unstructured":"Rinella ME, Lazarus JV, Ratziu V, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77:1797\u2013835.","journal-title":"Hepatology"},{"issue":"3","key":"567_CR7","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.jaad.2009.03.027","volume":"61","author":"A Menter","year":"2009","unstructured":"Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61(3):451\u201385.","journal-title":"J Am Acad Dermatol"},{"issue":"1","key":"567_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/art.39480","volume":"68","author":"JA Singh","year":"2016","unstructured":"Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1\u201326.","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"567_CR9","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/art.40726","volume":"71","author":"JA Singh","year":"2019","unstructured":"Singh JA, Guyatt G, Ogdie A, et al. 2018 American College of Rheumatology\/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Rheumatol. 2019;71(1):5\u201332.","journal-title":"Arthritis Rheumatol"},{"issue":"3","key":"567_CR10","first-page":"e0193074","volume":"13","author":"BFTM Vollenbroek","year":"2018","unstructured":"Vollenbroek BFTM, de Jong EMGJ, van de Kerkhof PCM, et al. Dermatological guidelines for monitoring methotrexate treatment reduce drug survival compared to rheumatological guidelines. PLoS ONE. 2018;13(3):e0193074.","journal-title":"PLoS ONE"},{"issue":"6","key":"567_CR11","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1002\/jmv.25064","volume":"90","author":"A Cordie","year":"2018","unstructured":"Cordie A, Kamel M, Elshazly M, et al. Comparing the efficiency of FIB-4, Egy-score, APRI, and GUCI in liver fibrosis staging in Egyptians with chronic hepatitis C. J Med Virol. 2018;90(6):1106\u201311.","journal-title":"J Med Virol"},{"issue":"2","key":"567_CR12","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1111\/liv.14669","volume":"41","author":"J Lee","year":"2021","unstructured":"Lee J, Vali Y, Boursier J, et al. Prognostic accuracy of FIB-4, MASLD fibrosis score, and APRI for MASLD-related events: a systematic review. Liver Int. 2021;41(2):261\u201370.","journal-title":"Liver Int"},{"key":"567_CR13","first-page":"21","volume":"8","author":"H Cheng","year":"2018","unstructured":"Cheng H, Rademaker M. Monitoring methotrexate-induced liver fibrosis in patients with psoriasis: utility of transient elastography. Psoriasis (Auckl). 2018;8:21\u20139.","journal-title":"Psoriasis (Auckl)"},{"key":"567_CR14","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1016\/j.eprac.2022.03.010","volume":"28","author":"K Cusi","year":"2022","unstructured":"Cusi K, Isaacs S, Barb D, et al. American Association of Clinical Endocrinology Clinical Practice Guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings. Endocr Pract. 2022;28:528\u201362.","journal-title":"Endocr Pract"},{"key":"567_CR15","doi-asserted-by":"publisher","first-page":"19275","DOI":"10.1038\/s41598-021-98776-1","volume":"11","author":"M Moini","year":"2021","unstructured":"Moini M, Hosseini M, Pourgholami MH, et al. Combination of FIB-4 with ultrasound surface nodularity or elastography as predictors of histologic advanced liver fibrosis in chronic liver disease. Sci Rep. 2021;11:19275.","journal-title":"Sci Rep"},{"key":"567_CR16","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.jhep.2022.12.034","volume":"78","author":"E Atallah","year":"2023","unstructured":"Atallah E, Smith M, Roudot-Thoraval F, et al. Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated. J Hepatol. 2023;78:989\u201397.","journal-title":"J Hepatol"},{"issue":"9","key":"567_CR17","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1002\/art.27584","volume":"62","author":"D Aletaha","year":"2010","unstructured":"Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569\u201381.","journal-title":"Arthritis Rheum"},{"issue":"9","key":"567_CR18","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1136\/annrheumdis-2016-210629","volume":"76","author":"JH Humphreys","year":"2017","unstructured":"Humphreys JH, Warner A, Costello R, Lunt M, Verstappen SMM, Dixon WG. Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate. Ann Rheum Dis. 2017;76(9):1509\u201314.","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"567_CR19","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1016\/j.jhep.2023.06.003","volume":"79","author":"ME Rinella","year":"2023","unstructured":"Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;79(6):1542\u201356.","journal-title":"J Hepatol"},{"issue":"6","key":"567_CR20","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/hep.21178","volume":"43","author":"RK Sterling","year":"2006","unstructured":"Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection. Hepatology. 2006;43(6):1317\u201325.","journal-title":"Hepatology"},{"issue":"5","key":"567_CR21","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/ajg.2016.453","volume":"112","author":"S McPherson","year":"2017","unstructured":"McPherson S, Hardy T, Henderson E, et al. Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis. Am J Gastroenterol. 2017;112(5):740\u201351.","journal-title":"Am J Gastroenterol"},{"issue":"17","key":"567_CR22","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1056\/NEJMra2403308","volume":"393","author":"L Castera","year":"2025","unstructured":"Castera L, Rinella ME, Tsochatzis EA. Noninvasive assessment of liver fibrosis. N Engl J Med. 2025;393(17):1715\u201329.","journal-title":"N Engl J Med"},{"issue":"4","key":"567_CR23","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/j.jhep.2010.07.033","volume":"54","author":"EA Tsochatzis","year":"2011","unstructured":"Tsochatzis EA, Gurusamy KS, Ntaoula S, et al. Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy. J Hepatol. 2011;54(4):650\u20139.","journal-title":"J Hepatol"},{"issue":"5","key":"567_CR24","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.jhep.2016.12.022","volume":"66","author":"T Karlas","year":"2017","unstructured":"Karlas T, Petroff D, Sasso M, et al. Individual patient meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017;66(5):1022\u201330.","journal-title":"J Hepatol"},{"issue":"2","key":"567_CR25","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/ajd.13546","volume":"62","author":"A Azzam","year":"2021","unstructured":"Azzam A, Jiyad Z, O\u2019Beirne J. Is methotrexate hepatotoxicity associated with cumulative dose? A systematic review and meta-analysis. Australas J Dermatol. 2021;62(2):130\u201340.","journal-title":"Australas J Dermatol"},{"key":"567_CR26","doi-asserted-by":"publisher","first-page":"152840","DOI":"10.1016\/j.tox.2021.152840","volume":"458","author":"D Ezhilarasan","year":"2021","unstructured":"Ezhilarasan D. Hepatotoxic potentials of methotrexate: understanding the possible toxicological molecular mechanisms. Toxicology. 2021;458:152840.","journal-title":"Toxicology"},{"key":"567_CR27","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.ejmech.2018.09.027","volume":"158","author":"W Wang","year":"2018","unstructured":"Wang W, Zhou H, Liu L. Side effects of methotrexate therapy for rheumatoid arthritis: a systematic review. Eur J Med Chem. 2018;158:502\u201316.","journal-title":"Eur J Med Chem"},{"key":"567_CR28","doi-asserted-by":"publisher","first-page":"1207999","DOI":"10.3389\/fphar.2023.1207999","volume":"14","author":"Y Shi","year":"2023","unstructured":"Shi Y, Shi L, Liu Q, Wang W, Liu Y. Molecular mechanism and research progress on pharmacology of ferulic acid in liver diseases. Front Pharmacol. 2023;14:1207999.","journal-title":"Front Pharmacol"},{"issue":"1","key":"567_CR29","doi-asserted-by":"publisher","first-page":"150","DOI":"10.55563\/clinexprheumatol\/usddjr","volume":"40","author":"J Avouac","year":"2022","unstructured":"Avouac J, Combe B, Dougados M, et al. Risk of liver fibrosis induced by methotrexate and other rheumatoid arthritis medications according to the Fibrosis-4 Index. Clin Exp Rheumatol. 2022;40(1):150\u20137.","journal-title":"Clin Exp Rheumatol"},{"key":"567_CR30","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.ejim.2023.08.002","volume":"118","author":"IA De la Rosa","year":"2023","unstructured":"De la Rosa IA, G\u00f3mez-Reino JJ, Carmona L, et al. Clinical features and immune mechanisms directly linked to the altered liver function in patients with rheumatoid arthritis. Eur J Intern Med. 2023;118:49\u201358.","journal-title":"Eur J Intern Med"},{"issue":"4","key":"567_CR31","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.3390\/jcm12041599","volume":"12","author":"Q Hu","year":"2023","unstructured":"Hu Q, Wang H, Xu T. Predicting hepatotoxicity associated with low-dose methotrexate using machine learning. J Clin Med. 2023;12(4):1599.","journal-title":"J Clin Med"},{"issue":"9","key":"567_CR32","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1111\/1756-185X.14147","volume":"24","author":"A Loganathan","year":"2021","unstructured":"Loganathan A, Kamalaraj N, El-Haddad C, Pile K. Systematic review and meta-analysis on prevalence of metabolic syndrome in psoriatic arthritis, rheumatoid arthritis and psoriasis. Int J Rheum Dis. 2021;24(9):1112\u201320.","journal-title":"Int J Rheum Dis"},{"key":"567_CR33","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X241271886","author":"JC Williams","year":"2024","unstructured":"Williams JC, Hum RM, Rogers K, et al. Metabolic syndrome and psoriatic arthritis: the role of weight loss as a disease-modifying therapy. Rheumatology (Oxford). 2024. https:\/\/doi.org\/10.1177\/1759720X241271886.","journal-title":"Rheumatology (Oxford)"},{"issue":"9","key":"567_CR34","doi-asserted-by":"publisher","first-page":"5090","DOI":"10.1093\/rheumatology\/keaf282","volume":"64","author":"F Kharouf","year":"2025","unstructured":"Kharouf F, Mehta P, Carrizo Abarza V, Gao S, Pereira D, Gladman DD, Poddubnyy D, Chandran V. The lack of association between cumulative MTX dose and liver fibrosis in PsA: a cohort study. Rheumatology (Oxford). 2025;64(9):5090\u20135. https:\/\/doi.org\/10.1093\/rheumatology\/keaf282.","journal-title":"Rheumatology (Oxford)"},{"issue":"2","key":"567_CR35","doi-asserted-by":"publisher","first-page":"keaf640","DOI":"10.1093\/rheumatology\/keaf640","volume":"65","author":"K Meridor","year":"2026","unstructured":"Meridor K, Harrison SR, Parker R, Chimakurthi C, Laws PM, McGonagle D, Barr A, Vandevelde CY, Marzo-Ortega H, Freeston JE. FIB-4 as an effective screening tool in psoriatic arthritis patients at high-risk for liver disease: a cross-sectional study using FibroScan. Rheumatology (Oxford). 2026;65(2):keaf640. https:\/\/doi.org\/10.1093\/rheumatology\/keaf640.","journal-title":"Rheumatology (Oxford)"},{"key":"567_CR36","doi-asserted-by":"crossref","unstructured":"Sung S, Newsome PN, Anstee QM, et al. Age-dependent differences in FIB-4 predictions of fibrosis in patients with MASLD referred from primary care. Hepatol Commun. 2025;9(1).","DOI":"10.1097\/HC9.0000000000000609"},{"issue":"10","key":"567_CR37","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1002\/hep4.1411","volume":"3","author":"T Davyduke","year":"2019","unstructured":"Davyduke T, Tandon P, Al-Karaghouli M, et al. Impact of implementing a FIB-4 First strategy on a pathway for patients with NAFLD referred from primary care. Hepatol Commun. 2019;3(10):1322\u201333.","journal-title":"Hepatol Commun"},{"issue":"11","key":"567_CR38","doi-asserted-by":"publisher","first-page":"2567","DOI":"10.1016\/j.cgh.2021.12.034","volume":"20","author":"I Graupera","year":"2022","unstructured":"Graupera I, Thiele M, Serra-Burriel M, et al. Low accuracy of FIB-4 and NAFLD fibrosis scores for screening for liver fibrosis in the population. Clin Gastroenterol Hepatol. 2022;20(11):2567\u201376.","journal-title":"Clin Gastroenterol Hepatol"}],"container-title":["Advances in Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s42358-026-00567-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42358-026-00567-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42358-026-00567-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:02:38Z","timestamp":1792522958000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s42358-026-00567-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["567"],"URL":"https:\/\/doi.org\/10.1186\/s42358-026-00567-7","relation":{},"ISSN":["2523-3106"],"issn-type":[{"value":"2523-3106","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]},"assertion":[{"value":"28 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the Research Ethics Committees (\n                      Comit\u00eas de \u00c9tica em\n                      Pesquisa \u2013 CEP) of all participating institutions (Faculdade Evang\u00e9lica Mackenzie do Paran\u00e1, Secretaria de Sa\u00fade de S\u00e3o Jos\u00e9 dos Pinhais and Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1) and conducted in accordance with the Declaration of Helsinki and Brazilian National Health Council Resolution No. 466\/12 (approval numbers: 7.922.034, 7.933.624 and 7.883.040). Written informed consent was obtained from all participants.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"59"}}