Serum Ferritin Levels and Liver-Related Events in Individuals With Steatotic Liver Disease: A Longitudinal Cohort Study

Abstract

Background

Serum ferritin has been suggested as a potential biomarker associated with disease progression in metabolic dysfunction–associated steatotic liver disease (MASLD).

Aims

We investigated the association between serum ferritin levels and liver-related events (LREs) in individuals with steatotic liver disease (SLD).

Methods

This cohort study included 17,560 adults with SLD (MASLD [n = 15,744], MASLD with increased alcohol intake (MetALD) [n = 1103] and cryptogenic SLD [n = 713]) without LRE at baseline. A steatotic liver was diagnosed using ultrasound, and LRE was defined as the development of decompensation (ascites, variceal bleeding and hepatic encephalopathy) or hepatocellular carcinoma. Participants were categorised into high (≥ 300 μg/L for males, ≥ 200 μg/L for females) or normal to low (< 300 μg/L for males, < 200 μg/L for females) ferritin levels.

Results

During 211,425 person-years of follow-up (median: 12.3 years), 74 incident LRE cases were identified, with 63 cases in MASLD, 10 in MetALD and 1 in cryptogenic SLD. The multivariable-adjusted hazard ratio (aHR) for LRE comparing individuals with high and normal-to-low ferritin level was 3.13 (95% confidence interval [CI] 1.89–5.18). Increased risk of LRE in individuals with high serum ferritin level compared to those with normal to low serum ferritin level was consistent across SLD subtypes (aHR 2.69, 95% CI 1.55–4.67 for MASLD; aHR 5.73, 95% CI 1.31–25.0 for MetALD), and SLD severity assessed by Fibrosis-4 (FIB-4) index (aHR 2.38, 95% CI 1.34–4.21 for FIB-4 ≥ 1.3; aHR 3.13, 95% CI 1.18–8.29 for FIB-4 < 1.3).

Conclusions

Serum ferritin levels correlated with the risk of LRE in patients with SLD.