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Non\u2010alcoholic fatty liver disease (NAFLD), prevalent liver disease in CKD patients, may limit EPO response because of thrombopoietin deficiency, iron homeostasis disorder and inflammation. Therefore, we hypothesized NAFLD is a risk factor for EPO responsiveness. To test our hypothesis, we evaluated the effect of EPO in healthy rats and rats with NAFLD induced by a high\u2010fat, high\u2010carbohydrate (HFHC) diet. After 12\u2009weeks on the HFHC diet, NAFLD rats showed lower erythroid response to EPO treatment than healthy rats. We, then, determined that the primary cause of EPO hyporesponsiveness could be iron deficiency associated with inflammation, which reduces erythroid cell production. Specifically, the concentrations of hepcidin, ferritin, transferrin and white blood cells in NAFLD rats were 12.8\u2010, 16.4\u2010, 2.51\u2010 and 1.40\u2010fold higher than those in healthy rats, respectively. However, erythroid cell types in the bone marrow of NAFLD rats were significantly reduced. In conclusion, our data suggest that NAFLD could be a risk factor for EPO responsiveness, which is attributed to functional iron deficiency associated with inflammation.<\/jats:p>","DOI":"10.1111\/1440-1681.13869","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T05:14:02Z","timestamp":1715318042000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Erythropoietin hyporesponsiveness in non\u2010alcoholic fatty liver disease"],"prefix":"10.1111","volume":"51","author":[{"given":"Huixi","family":"Zou","sequence":"first","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine The Chinese University of Hong Kong  Shatin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond S. 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