{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:47Z","timestamp":1787026667089,"version":"build-2736575974"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"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>Objective<\/jats:title>\n                    <jats:p>Liver diseases represent a major global health burden. Growth Differentiation Factor 15 (GDF-15), a stress-induced cytokine, has been suggested to protect against fibrosis progression through neuro-metabolic-immunologic pathways and to regulate energy and lipid homeostasis, potentially influencing hepatic steatosis. This study evaluated the role of GDF-15 in steatosis and fibrosis, considering prior liver injury, alcohol intake, insulin resistance, and obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and methods<\/jats:title>\n                    <jats:p>In this retrospective cohort study, 626 participants from a large population-based cohort were analyzed. Associations of baseline GDF-15, alcohol intake, FIB-4 score, and metabolic risk factors with hepatic steatosis and fibrosis over 6 years were examined using linear regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In participants with elevated baseline FIB-4, the interaction of GDF-15 and FIB-4 was positively associated with follow-up liver stiffness (\u03b2 = 0.47,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.045). Interactions between GDF-15 and higher alcohol intake (3rd\/4th quantiles) were negatively associated with stiffness (\u03b2 = \u22121.68, p = 0.002; \u03b2 = \u22121.43,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.038). GDF-15 was positively associated with follow-up steatosis (\u03b2 = 37.14,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.006). Higher HOMA-IR (3rd\/4th quantile) was linked to increased steatosis (\u03b2 = 31.15,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.032; \u03b2 = 38.15, p = 0.023), whereas interactions of HOMA-IR \u00d7 GDF-15 were inversely associated (\u03b2 = \u221238.98,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.008; \u03b2 = \u221238.54,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.019), suggesting a protective modulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GDF-15 appears to modulate hepatic steatosis and fibrosis in individuals with metabolic or lifestyle risk factors, supporting its potential as a therapeutic target and warranting further investigation of the neuro-metabolic-immunologic axis.<\/jats:p>\n                  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