The serum hepcidin and the hepcidin/ferritin ratio in NAFLD: a systematic review and meta-analysis

• Published in: BMC gastroenterology Vol. 25; no. 1; pp. 62 - 13
• Main Authors: Song, Jingmin, Wang, Heqing, Gao, Xiaolian, Yang, Fen, Zhu, Xinhong, Qiao, Guiyuan, Gan, Ting, Tao, Junxiu
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.02.2025; BioMed Central; BMC
• Subjects: Adult; Analysis; Biomarkers; Biomarkers - blood; Body mass index; Clinical trials; Development and progression; Fatty liver; Female; Ferritin; Ferritins - blood; Hepcidin; Hepcidin/ferritin ratio; Hepcidins - blood; Humans; Inflammation; Iron; Liver; Liver diseases; Male; Medical research; Medical Subject Headings-MeSH; Medicine, Experimental; Meta-analysis; Metabolism; NAFLD; Non-alcoholic Fatty Liver Disease - blood; Pathogenesis; Peptides; Physiological aspects; Proteins; Statistical analysis; Steatosis; Systematic review; NAFLD; Hepcidin; Hepcidin/ferritin ratio; Meta-analysis
• DOI: 10.1186/s12876-025-03620-9
• ISSN: 1471-230X

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver diseases characterized by hepatic steatosis exceeding 5% in the absence of alcohol and other liver-damaging factors. Clinical studies have identified a potential link between abnormal iron metabolism and the high incidence of NAFLD; however, the results from clinical trials remain inconsistent. This meta-analysis aims to compare serum hepcidin levels and the hepcidin/ferritin ratio between adults with NAFLD and those without to explore their potential relationship with NAFLD. A systematic search was conducted across the Web of Science platform, Cochrane, Scopus, Embase, and PubMed databases from their inception until December 18, 2024. The analysis primarily focused on serum hepcidin levels and the hepcidin/ferritin ratio. Observational studies comparing serum hepcidin levels and the hepcidin/ferritin ratio between individuals with NAFLD and control groups were included. A random-effects model was employed to calculate effect estimates, and outcomes were reported as standardized mean differences (SMD) with 95% confidence intervals (95% CI). Following the systematic review, a total of 19 studies, comprising 2216 patients and 2125 controls, were included. The findings revealed a statistically significant difference in both hepcidin levels (SMD = 1.03, 95% CI: 0.49 to 1.56, p < 0.001) and the hepcidin/ferritin ratio (SMD = -1.13, 95% CI: -1.79 to -0.46, p < 0.001) between NAFLD and controls. Significant heterogeneity was observed across studies for both hepcidin (I² = 98.2%) and the hepcidin/ferritin ratio (I² = 93.3%), and the limited number of studies on hepcidin/ferritin were acknowledged as key limitations. Subgroup analysis revealed that patients with obesity exhibited higher levels of hepcidin (SMD = 1.12, 95% CI: 0.40 to 1.97) than overweight (SMD = 0.88, 95% CI: 0.05 to 1.72). Meta-regression analysis identified the hepcidin measurement method (p < 0.01), male-to-female ratio (p < 0.01), and study quality (p < 0.01) as significant moderators of the observed heterogeneity. This meta-analysis revealed a significant association between hepcidin levels, the hepcidin/ferritin ratio and NAFLD in adults. Further investigations are needed to fully elucidate the role of these variables in iron metabolism and their potential impact on the diagnosis, prevention, and management of NAFLD.