Liver Iron Content in Individuals With B-Thalassemia Trait and Hyperferritinemia: Role of Metabolic Alterations, HFE Genotypes, and Cirrhosis

Background: An increased serum ferritin is a frequent finding in adults with β-thalassemia trait (BTT). However, whether such an increase is associated with a proportional increase in iron stores is unclear. Objectives. We aimed to evaluate liver iron stores in a consecutive cohort of BTT with hyperferritinemia who underwent magnetic resonance imaging (LICMRI) for clinical purposes. Methods. Sixty-six BTT subjects with hyperferritinemia were studied. Clinical, biochemical, and genetic evaluations were done to assess the cause of hyperferritinemia. LICMRI was classified as: grade-1 = ≤3 mg/g (normal/mild); grade-2 = >3 ≤7 mg/g (moderate); grade-3 = >7 (severe). Results. 80.3% showed normal/mild (n=29, 43.9%) or moderate LICMRI (n=24, 36.4%), while 19.7% (n=13) showed values >7 mg/g. The latter had lower haemoglobin concentration (p=0.004) and higher transferrin saturation and ferritin compared to subjects with lower LICMRI (p<0.001), while steatotic liver disease was more frequent in subjects with lower LICMRI grades (p=0.012). Liver cirrhosis was significantly more frequent in subjects with moderate/severe than in those with lower LICMRI grades (p=0.001 and p=0.025, respectively). We found a higher frequency of HFE and non-HFE iron-related genotypes (risk genotypes) in LICMRI grades 2-3 compared to none in LICMRI grade 1 (p=0.003 and p<0.0001, respectively). A regression analysis identified risk genotypes, liver cirrhosis, and BMI as significantly associated with LICMRI. Conclusions. Hyperferritinemia is common in BTT subjects, but major iron overload is limited to a minority of cases. They present associated genetic and acquired causes of iron accumulation and increased risk of liver damage.