The burden of liver disease continues to increase in the UK, with liver cirrhosis reported to be the third most common cause of premature death. Iron overload, a condition that impacts liver health, was traditionally associated with genetic disorders such as hereditary haemochromatosis, however, it is now increasingly associated with obesity, type-2 diabetes and non-alcoholic fatty liver disease.

The aim of this study was to assess the prevalence of elevated levels of liver iron within the UK Biobank imaging study in a cohort of 9108 individuals. Magnetic resonance imaging (MRI) was undertaken at the UK Biobank imaging centre, acquiring a multi-echo spoiled gradient-echo single-breath-hold MRI sequence from the liver.

All images were analysed for liver iron and fat (expressed as proton density fat fraction or PDFF) content using LiverMultiScan. Liver iron was measured in 97.3% of the cohort. The mean liver iron content was 1.32 ± 0.32 mg/g while the median was 1.25 mg/g (min: 0.85 max: 6.44 mg/g).

Overall 4.82% of the population were defined as having elevated liver iron, above commonly accepted 1.8 mg/g threshold based on biochemical iron measurements in liver specimens obtained by biopsy.

Further analysis using univariate models showed elevated liver iron to be related to male sex (p<10-16, r2 = 0.008), increasing age (p<10-16, r2 = 0.013), and red meat intake (p<10-16, r2 = 0.008). Elevated liver fat (>5.6% PDFF) was associated with a slight increase in prevalence of elevated liver iron (4.4% vs 6.3%, p = 0.0007).

This study shows that population studies including measurement of liver iron concentration are feasible, which may in future be used to better inform patient stratification and treatment.

Ethnicity appeared to have a small yet significant impact of liver iron levels, which were significantly elevated in Caucasian compared with Asian subjects. Given the differences in the median values are very small, this may not be clinically significant, however reports of hemochromatosis within Asian populations are low, therefore the impact of ethnicity of liver iron levels may warrant further investigation.

There was a very weak relationship between liver iron and BMI, with prevalence of elevated liver iron levels being less common in subjects with a BMI less than 20 kg/m2. Relatively few studies have explored the relationship between BMI and elevated liver iron levels and available data are conflicting.

Liver iron and BMI

Zheng et al reported a positive association between liver iron and BMI; however, this is at odds with the findings of Nelson et al who reported lower BMI to be associated with increased liver iron.

These differences may be accounted for by the fact that our cohort was comprised from relatively healthy subjects from the general population whereas previous studies had a disease positive NASH cohort.

A relationship between self-reported frequency of beef consumption of liver iron was observed. It is established that there is a significant relationship between red meat consumption and serum ferritin levels, and that overfeeding animals with dietary iron causes an increase in liver iron.

Furthermore, there is a positive association between red meat intake and liver cancer and chronic liver disease. Although the results presented here are preliminary, the UK Biobank data will allow further investigation of the impact of other dietary factors which have been suggested to have an influence on liver iron and liver health outcomes.