Hyperferritinemia is associated with higher liver-related event incidence in patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: Hyperferritinemia (HF), defined as elevated serum ferritin (SF) levels, can reflect iron stores and chronic inflammation. However, the prevalence and clinical features of HF in metabolic dysfunction-associated steatotic liver disease (MASLD) have not been systematically evaluated. This systematic review and meta-analysis aimed to examine this topic. METHODS: PubMed and Embase were searched from inception to December 2, 2024 for observational studies reporting the prevalence and/or impact of HF (under any definition) in MASLD diagnosed by liver biopsy, imaging, or biomarkers. Meta-analysis was performed using random-effects modelling to obtain pooled proportions, odds/hazard ratios (HRs), and mean differences. PROSPERO ID: CRD420250656514. RESULTS: We identified 16 studies, involving 49 754 patients with MASLD. The pooled prevalence of HF in MASLD was 26.36% (95% CI 21.03 to 32.49, I = 99.2%), highest in Asia (30.89%) and lowest in North America (20.22%). Prevalence was greater among biopsy-proven MASLD (32.61%) and similar (24.87%) when restricted to studies using the consensus definition of HF. Compared with non-HF patients, MASLD-HF patients were more likely to be male and exhibited higher levels of triglycerides, HbA1c, insulin resistance, and liver enzymes. HF was associated with features of advanced liver disease, including steatohepatitis and significant fibrosis, and was associated with a higher incidence of liver-related events (HR 2.02, 95% CI 1.50 to 2.71; I = 0%). CONCLUSIONS: HF is present in approximately one in four patients with MASLD and identifies a subgroup with more severe metabolic dysfunction and liver injury. These data highlight SF as a simple, accessible biomarker that may help identify higher-risk MASLD phenotypes.