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Breastfeeding in infancy was ascertained via self-report. In a cross\u2011sectional analysis involving 26,850 participants with liver MRI data, metabolic dysfunction-associated steatotic liver disease (MASLD) was defined as PDFF\u2009&gt;\u20095.5%, and MASH as PDFF\u2009&gt;\u20095.5% combined with cT1\u2009&gt;\u2009800 ms. Additionally, a longitudinal analysis of 378,702 participants assessed associations with incident cirrhosis, hepatocellular carcinoma (HCC), and liver\u2011related mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In MRI-based analysis, breastfeeding in infancy was associated with lower odds of MASLD (OR 0.89, 95% CI 0.80\u20130.99) and MASH (OR 0.79, 95% CI 0.65\u20130.97) in females but not males, with a significant sex interaction for MASH (P for interaction\u2009=\u20090.023) but not for MASLD (P for interaction\u2009=\u20090.301). Over a median follow\u2011up of 14.9 years, breastfeeding was associated with reduced risks of cirrhosis (HR 0.71, 95% CI 0.60\u20130.83), HCC (HR 0.52, 95% CI 0.33\u20130.82), and liver\u2011related mortality (HR 0.63, 95% CI 0.46\u20130.86) in females. No such associations were observed in males (P for interaction\u2009=\u20090.047, 0.030, and 0.008, respectively). Mediation analysis revealed that circulating insulin-like growth factor-1 (IGF-1) mediated the association specifically in females, with a sex difference in the indirect effect (FDR\u2009&lt;\u20090.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Breastfeeding in infancy confers a long-term protective effect against MASH and adverse liver outcomes in women, but not in men. This sex-specific protective association was mediated by circulating IGF-1, suggesting a potential underlying mechanism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-026-00919-4","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T23:04:02Z","timestamp":1778540642000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Breastfeeding in infancy confers sex-specific, long-term protection against metabolic dysfunction-associated steatohepatitis and adverse liver outcomes"],"prefix":"10.1186","volume":"17","author":[{"given":"Huiyi","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haobin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinfeng","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maolong","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaifeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"issue":"4","key":"919_CR1","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","volume":"77","author":"ZM Younossi","year":"2023","unstructured":"Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. 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