Serum ferritin level is associated with liver fibrosis and incident liver-related outcomes independent of HFE genotype in the general population

Abstract

Background & Aims

Hyperferritinemia reflects iron accumulation in the body and has been associated with metabolic disturbances and alcohol use, and is also a common finding in individuals diagnosed with liver disease. The major genetic regulator of iron metabolism is the HFE gene.

Methods

The aim of this this study was to investigate the association between serum ferritin and liver fibrosis using the enhanced liver fibrosis (ELF) test, and the association between ferritin and liver-related outcomes in a Finnish population-based cohort of 6194 individuals (45% male, mean [± standard deviation] age, 52.9 ± 14.9 years; body mass index 26.9 ± 4.7 kg/m²). The effects of HFE variants on these associations were also evaluated.

Results

Serum ferritin levels were significantly associated with liver fibrosis, as estimated by enhanced liver fibrosis (ELF) test in weighted linear regression analysis. Serum ferritin was significantly associated with both all liver-related outcomes (n = 92) and severe liver-related outcomes (n = 54) in weighted Cox regression analysis (hazard ratio [HR] per 1 SD, 1.11 [95% confidence interval (CI) 1.02–1.21]; p = 0.012 and HR 1.11 [95% CI 1.02–1.21]; p = 0.013, respectively). However, there was association neither between HFE risk variants and ELF test nor between HFE risk variants and liver-related outcomes.

Conclusion

Serum ferritin levels were associated with liver fibrosis and incident liver disease, independent of HFE genotype in the general population. Furthermore, data demonstrated that metabolic disturbances and alcohol use were major risk factors for hyperferritinemia.

Keywords:

• Advanced liver disease
• cirrhosis
• iron
• hyperferritinemia

Acknowledgements

The samples/data used for the research were obtained from THL Biobank (study numbers: BB2016_98, BB2017_101 and BB2019_31). We thank all study participants for their generous participation in THL Biobank and the Health 2000 Survey. We thank Siemens Healthineers for supplying reagents and consumables needed to conduct ELF testing.

Disclosure statement

The authors have no financial disclosures or conflicts of interest to declare.

Data availability statement

Health 2000 Survey data are available from the THL Biobank based on a research application, as explained on the website of the THL Biobank (https://thl.fi/en/web/thl-biobank/for-researchers).

Additional information

Funding

VM was supported by the Finnish Medical Foundation, State Research funding (VTR) from Kuopio University Hospital and Mary and Georg Ehrnrooth Foundation. FÅ was supported by the Academy of Finland (#338544), Sigrid Jusélius Foundation, Svenska Kulturfonden, Wilhelm and Else Stockmann Foundation, and Finska Läkaresällskapet.