{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:12:56Z","timestamp":1778649176463,"version":"3.51.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease globally, and the accurate assessment of hepatic fibrosis is crucial for guiding therapeutic decisions. This study aimed to investigate the diagnostic value of the interaction between the platelet-to-lymphocyte ratio (PLR) and the Fibrosis-4 (FIB-4) index for predicting significant hepatic fibrosis in patients with MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study analyzed 358 MASLD patients who underwent liver biopsy at two university-affiliated hospitals between January 2020 and December 2024. Based on histopathology, significant fibrosis was defined as fibrosis stage \u2265F2. Four predictive models were constructed: PLR alone, FIB-4 alone, a combined PLR\u202f+\u202fFIB-4 model, and a PLR\u202f\u00d7\u202fFIB-4 interaction model. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI), and compared against traditional non-invasive scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 358 patients, 168 (46.9%) had significant fibrosis. PLR was positively correlated with the FIB-4 index (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f0.542,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), and this correlation strengthened with increasing fibrosis severity. The interaction model demonstrated the best diagnostic performance, yielding an AUC of 0.824 (95% CI: 0.778\u20130.870) for significant fibrosis, with 78.6% sensitivity and 78.9% specificity. For predicting advanced fibrosis (\u2265F3), its AUC was 0.852 (95% CI: 0.803\u20130.901). Compared to the APRI-FIB-4 composite score, the interaction model significantly improved reclassification (NRI: 0.142,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.008) and discrimination (IDI: 0.067,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.003). A three-tier risk stratification strategy based on the model also showed excellent clinical utility (\n                      <jats:italic>p<\/jats:italic>\n                      for trend &amp;lt;0.001). Bootstrap internal validation (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f1,000) confirmed the model\u2019s stability and calibration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The PLR\u202f\u00d7\u202fFIB-4 interaction model is a novel and effective tool for the non-invasive assessment of hepatic fibrosis in patients with MASLD. This model significantly outperforms individual markers and traditional scoring systems and demonstrates excellent risk stratification capability, holding significant promise for supporting individualized clinical management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1804716","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:44:46Z","timestamp":1778647486000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Interactive effects of platelet-to-lymphocyte ratio and FIB-4 index for risk stratification of liver fibrosis in metabolic dysfunction-associated steatotic liver disease: performance assessment comparing interactive models with traditional composite scores"],"prefix":"10.3389","volume":"13","author":[{"given":"Mei","family":"Shi","sequence":"first","affiliation":[{"name":"Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine","place":["Shenzhen, China"]},{"name":"Department of Infectious Diseases, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangdong","family":"Tong","sequence":"additional","affiliation":[{"name":"Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine","place":["Shenzhen, China"]},{"name":"Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1053\/j.gastro.2015.04.043","article-title":"Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease","volume":"149","author":"Angulo","year":"2015","journal-title":"Gastroenterology"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1053\/j.gastro.2005.03.084","article-title":"Sampling variability of liver biopsy in nonalcoholic fatty liver disease","volume":"128","author":"Ratziu","year":"2005","journal-title":"Gastroenterology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1007\/s00125-016-3902-y","article-title":"EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver 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Comparison with liver biopsy and fibrotest","volume":"46","author":"Vallet-Pichard","year":"2007","journal-title":"Hepatology"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1136\/gut.2010.216077","article-title":"Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease","volume":"59","author":"McPherson","year":"2010","journal-title":"Gut"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1002\/sim.2929","article-title":"Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond","volume":"27","author":"Pencina","year":"2008","journal-title":"Stat Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of MASLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat 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An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann N Y Acad Sci"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/hep.24105","article-title":"Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis","volume":"53","author":"Lin","year":"2011","journal-title":"Hepatology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/nrgastro.2018.10","article-title":"Noninvasive imaging biomarker assessment of liver fibrosis by elastography in MASLD","volume":"15","author":"Tapper","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1053\/j.gastro.2018.12.036","article-title":"Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease","volume":"156","author":"Castera","year":"2019","journal-title":"Gastroenterology"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.jhep.2016.06.005","article-title":"MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in MASLD and MASLD: clinical trials to clinical practice","volume":"65","author":"Dulai","year":"2016","journal-title":"J Hepatol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/S2468-1253(19)30383-8","article-title":"FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study","volume":"5","author":"Newsome","year":"2020","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.jhep.2021.05.025","article-title":"EASL clinical practice guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 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