Circulating Ferritin in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Eleftheria Makri; Myrsini Orfanidou; Evangelia S Makri; Antonis Goulas; Evangelos Terpos; Stergios A Polyzos

doi:10.1016/j.jceh.2024.101353

Circulating Ferritin in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

J Clin Exp Hepatol. 2024 May-Jun;14(3):101353. doi: 10.1016/j.jceh.2024.101353. Epub 2024 Feb 2.

Authors

Eleftheria Makri¹, Myrsini Orfanidou¹, Evangelia S Makri¹, Antonis Goulas¹, Evangelos Terpos², Stergios A Polyzos¹

Affiliations

¹ First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
² Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

PMID: 38435724
PMCID: PMC10905002 (available on 2025-05-01)
DOI: 10.1016/j.jceh.2024.101353

Abstract

Objectives: To synthesize data on circulating ferritin between patients with histologically confirmed nonalcoholic fatty liver disease (NAFLD) and non-NAFLD controls.

Methods: A systematic literature search was conducted in PubMed, Scopus, and the Cochrane Library. Thirty-one studies comprising data on 5631 individuals (2929 biopsy-proven NAFLD patients and 2702 controls) were included in the meta-analysis.

Results: Higher circulating ferritin levels were observed in NAFLD patients than in controls [standardized mean difference (SMD) 1.14; 95% confidence interval (95% CI) 0.73-1.55], in patients with simple nonalcoholic fatty liver (NAFL) than in controls (SMD 0.57; 95% CI 0.34-0.80), in patients with nonalcoholic steatohepatitis (NASH) than in controls (SMD 0.95; 95% CI 0.69-1.22), and in NASH than in NAFL patients (SMD 0.62; 95% CI 0.25-0.99). There was moderate-to-high heterogeneity among studies in the above pairs of comparisons (I² = 68-97%); no risk of publication bias was observed by Egger's test (P = 0.81, P = 0.72, P = 0.59, P = 0.42, respectively). The heterogeneity was reduced in the subgroup of biopsy-proven controls in all pairs of comparisons (I² = 0-65%). The heterogeneity was also reduced after excluding studies with the Newcastle-Ottawa Scale (NOS) score <7 (n = 10) for the comparison of NAFLD patients vs. controls (I² = 54%, P = 0.02). The meta-regression analysis revealed that the male ratio was positively associated with ferritin SMD in the comparison between NAFLD patients and controls and accounted for 32.7% (P = 0.002) of the heterogeneity in this pair of comparison.

Conclusions: Circulating ferritin was higher in NAFLD (or NAFL or NASH) patients compared with controls. Higher levels of circulating ferritin were also associated with the severity of the disease, which, however, should be cautiously interpreted.PROSPERO registration ID: CRD42022354025.

Keywords: ferritin; iron; metabolic syndrome; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis.

Publication types

Review