Original Articles
Vol. 18 No. 1 (2026): Mediterranean Journal of Hematology and Infectious Diseases
https://doi.org/10.4084/MJHID.2026.051

LIVER IRON CONTENT IN INDIVIDUALS WITH LIVER IRON CONTENT IN INDIVIDUALS WITH Β-THALASSEMIA TRAIT AND HYPERFERRITINEMIA: ROLE OF METABOLIC ALTERATIONS, HFE GENOTYPES, AND CIRRHOSIS.: ROLE OF METABOLIC ALTERATIONS, HFE GENOTYPES, AND CIRRHOSIS.

Β-THALASSEMIA TRAIT AND HYPERFERRITINEMIA

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Published: June 30, 2026
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Iron overload, beta thalassemia minor, hyperferritinemia, Magnetic Resonance Imaging

Authors

Alberto Piperno
alberto.piperno@unimib.it
University of Milano-Bicocca, Monza, Italy, Italy.

Background. 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 the assessment of liver iron concentration by magnetic resonance (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 hemoglobin concentration (p=0.004) and higher transferrin saturation and ferritin compared to subjects with lower LICMRI (p<0.001), while steatotic liver disease were 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 (risky 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 risky 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.

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Ethics Approval

The manuscript is in accordance with ethical standards stated in the 1964 Declaration of Helsinki and its later amendments. Informed written consent for molecular testing and data recording in the local database was obtained from all the participants and collected according to the Institutional rules., Hyperferritinemia is common in BTT, but it is not known how related it is to LIC. We evaluated LIC by MRI in 66 consecutive subjects with BTT and hyperferritinemia 80% of subjects showed normal or mild/moderate LIC and 20% showed LIC > 7 mg/g Fatty liver was more common in the lower grades of LIC Iron-related genotypes and cirrhosis were more prevalent in those with LIC > 7mg/g.

Supporting Agencies

Grant Support: G.R. was funded by the European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS project code PNRR-MAD-2022-12376033, title “Evidence-based models for high impact chronic disease prevention and risk of progression management in outpatient community services and community hospitals: towards eHealth integrating stratification on individual history with predictive models of disease progression, using machine learning and artificial intelligence on administrative and clinical databases”, PI Antonio Giampiero Russo. S.G. participated in the manuscript preparation during their personal involvement in the Italian Ministry of University MUR Dipartimenti di Eccellenza 2023-2027 (l. 232/2016, art. 1, commi 314–337). S.G. was partially supported by the grant PRIN 2022SYXEH.
Alberto Piperno, University of Milano-Bicocca, Monza, Italy

Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

Centro Ricerca Tettamanti, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.

Full professor of Medical Genetics 

How to Cite



“LIVER IRON CONTENT IN INDIVIDUALS WITH LIVER IRON CONTENT IN INDIVIDUALS WITH Β-THALASSEMIA TRAIT AND HYPERFERRITINEMIA: ROLE OF METABOLIC ALTERATIONS, HFE GENOTYPES, AND CIRRHOSIS.: ROLE OF METABOLIC ALTERATIONS, HFE GENOTYPES, AND CIRRHOSIS.: Β-THALASSEMIA TRAIT AND HYPERFERRITINEMIA” (2026) Mediterranean Journal of Hematology and Infectious Diseases, 18(1), p. e2026051. doi:10.4084/MJHID.2026.051.
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