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

Abstract Background 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...

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Main Authors: Jingmin Song, Heqing Wang, Xiaolian Gao, Fen Yang, Xinhong Zhu, Guiyuan Qiao, Ting Gan, Junxiu Tao
Format: Article
Language:English
Published: BMC 2025-02-01
Series:BMC Gastroenterology
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Online Access:https://doi.org/10.1186/s12876-025-03620-9
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author Jingmin Song
Heqing Wang
Xiaolian Gao
Fen Yang
Xinhong Zhu
Guiyuan Qiao
Ting Gan
Junxiu Tao
author_facet Jingmin Song
Heqing Wang
Xiaolian Gao
Fen Yang
Xinhong Zhu
Guiyuan Qiao
Ting Gan
Junxiu Tao
author_sort Jingmin Song
collection DOAJ
description Abstract Background 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. Methods 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). Results 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. Conclusion 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.
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spelling doaj-art-6c3d8b3329db45a29b611eaede4a62ff2025-02-09T12:39:41ZengBMCBMC Gastroenterology1471-230X2025-02-0125111310.1186/s12876-025-03620-9The serum hepcidin and the hepcidin/ferritin ratio in NAFLD: a systematic review and meta-analysisJingmin Song0Heqing Wang1Xiaolian Gao2Fen Yang3Xinhong Zhu4Guiyuan Qiao5Ting Gan6Junxiu Tao7School of Nursing, Hubei University of Chinese MedicineSchool of Nursing, Hubei University of Chinese MedicineSchool of Nursing, Hubei University of Chinese MedicineSchool of Nursing, Hubei University of Chinese MedicineSchool of Nursing, Hubei University of Chinese MedicineSchool of Nursing, Hubei University of Chinese MedicineSchool of Nursing, Hubei University of Chinese MedicineHepatic Disease Institute, Hubei Key Laboratory of Theoretical and Applied Research of Liver and Kidney in Traditional Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese MedicineAbstract Background 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. Methods 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). Results 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. Conclusion 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.https://doi.org/10.1186/s12876-025-03620-9NAFLDHepcidinHepcidin/ferritin ratioMeta-analysis
spellingShingle Jingmin Song
Heqing Wang
Xiaolian Gao
Fen Yang
Xinhong Zhu
Guiyuan Qiao
Ting Gan
Junxiu Tao
The serum hepcidin and the hepcidin/ferritin ratio in NAFLD: a systematic review and meta-analysis
BMC Gastroenterology
NAFLD
Hepcidin
Hepcidin/ferritin ratio
Meta-analysis
title The serum hepcidin and the hepcidin/ferritin ratio in NAFLD: a systematic review and meta-analysis
title_full The serum hepcidin and the hepcidin/ferritin ratio in NAFLD: a systematic review and meta-analysis
title_fullStr The serum hepcidin and the hepcidin/ferritin ratio in NAFLD: a systematic review and meta-analysis
title_full_unstemmed The serum hepcidin and the hepcidin/ferritin ratio in NAFLD: a systematic review and meta-analysis
title_short The serum hepcidin and the hepcidin/ferritin ratio in NAFLD: a systematic review and meta-analysis
title_sort serum hepcidin and the hepcidin ferritin ratio in nafld a systematic review and meta analysis
topic NAFLD
Hepcidin
Hepcidin/ferritin ratio
Meta-analysis
url https://doi.org/10.1186/s12876-025-03620-9
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