Table 1.

Main clinical, biochemical, and imaging elements for the suspicion of HC

Leading
TSAT >45% (mainstay)
S-Ferritin >200 µg/L (females) or >300 µg/L (males)
Imaging evidence of liver IO (MRI* and/or biopsy†)
Iron deposits in hepatocytes (if biopsy is performed)
Absence of “predominant” acquired risk factors for hepcidin deficiency (eg, alcohol abuse or end-stage liver disease) and iatrogenic IO (eg, regular transfusions)
Absence of hematological signs of a primary RBC disorder, such as anemia‡ and/or reticulocytosis
Not always present
Signs and/or symptoms associated with IO:
• Skin pigmentation, asthenia
• Persistent increase of aminotransferases, hepatomegaly, cirrhosis, hepatocellular carcinoma
• Joint pain, arthritis, chondrocalcinosis, reduced bone mineral density
• Diabetes mellitus, hypopituitarism, hypoparathyroidism, hypogonadotropic hypogonadism
• Cardiomyopathy, heart failure, cardiac arrhythmias

TSAT, transferrin saturation; IO, iron overload; MRI, magnetic resonance imaging.

^*Liver iron concentration (LIC) by MRI can be obtained using different protocols, which vary depending on local expertise and equipment. With these limitations, any LIC value higher than the upper normal limit (generally set at 36 µmol/g to 40 µmol/g dry weight) should lead to consideration of phlebotomies in HC patients. Similarly, LIC >100 µmol/g to 120 µmol/g and >240 µmol/g to 300 µmol/g are generally considered as overt and severe IO, respectively (see text and references.^{55, 56}).

^†Liver biopsy should be considered in patients with ferritin >1000 µg/L or signs of liver damage.

^‡Exceptions may occur (eg, in HC patients with diagnosis delayed after the appearance of liver cirrhosis, in whom anemia may be observed because of hypersplenism or gastrointestinal bleeding, or subjects with β-thalassemia trait, whose coexistence is not rare in Mediterranean countries).