Page 51 - EASL POSTGRADUATE COURSE
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o Hypotheses to be discussed depending on HIC assessment:
Normal HIC:
§ If mild increase of serum ferritin levels (<500 μg/L; normal <400 μg/L): dysmetabolic
hyperferritinemia with no iron excess is likely.
§ If significantly increased serum ferritin levels (>500 μg/L): genetic hyperferritinemia should
be discussed in the absence of confounding factors such as inflammation, cell necrosis and
alcohol consumption.
Increased HIC:
§ If HIC exceeds 150 µmol/g dry weight, after ruling out a false positive (frequent due to MRI
artefacts): ferroportin disease should be discussed.
§ If HIC ranges between the upper limit of normal and 150 µmol/g dry weight: DIOS is likely.
DIOS is defined as the presence of unexplained hepatic iron excess in the setting of various features
of the MetS. Usually the patient is a middle-aged male with no or non-specific symptoms. Transferrin
saturation is not elevated. Hepatic iron excess is mild (<150 µmol/g) and located in both hepatocytes
and Kupffer cells with frequent iron deposition in spleen during MRI. NAFLD is associated in half of
the cases and significant fibrosis is found in 10-15% of patients.
Pathophysiology [4-9]
Development of iron excess (Fig. 1). In DIOS, abnormalities of iron metabolism evolve according
to a dynamic process with close interactions between the liver and VAT. Iron accumulates within the
liver, resulting in increased production of hepcidin, the key regulator of systemic iron. At the same time,
fatty acids accumulate in VAT resulting in abnormal production of cytokines, especially impairment
of adiponectin synthesis, leading to IR. IR enhances hepcidin production through glucose, insulin and
neoglucogenesis. This contributes to decreased hepatic iron excess, which could explain why hepatic
iron excess is frequent in patients who are overweight and rare in those who are obese.
Figure 1. Schematic hypothesis for the development of DIOS. 51
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015
Normal HIC:
§ If mild increase of serum ferritin levels (<500 μg/L; normal <400 μg/L): dysmetabolic
hyperferritinemia with no iron excess is likely.
§ If significantly increased serum ferritin levels (>500 μg/L): genetic hyperferritinemia should
be discussed in the absence of confounding factors such as inflammation, cell necrosis and
alcohol consumption.
Increased HIC:
§ If HIC exceeds 150 µmol/g dry weight, after ruling out a false positive (frequent due to MRI
artefacts): ferroportin disease should be discussed.
§ If HIC ranges between the upper limit of normal and 150 µmol/g dry weight: DIOS is likely.
DIOS is defined as the presence of unexplained hepatic iron excess in the setting of various features
of the MetS. Usually the patient is a middle-aged male with no or non-specific symptoms. Transferrin
saturation is not elevated. Hepatic iron excess is mild (<150 µmol/g) and located in both hepatocytes
and Kupffer cells with frequent iron deposition in spleen during MRI. NAFLD is associated in half of
the cases and significant fibrosis is found in 10-15% of patients.
Pathophysiology [4-9]
Development of iron excess (Fig. 1). In DIOS, abnormalities of iron metabolism evolve according
to a dynamic process with close interactions between the liver and VAT. Iron accumulates within the
liver, resulting in increased production of hepcidin, the key regulator of systemic iron. At the same time,
fatty acids accumulate in VAT resulting in abnormal production of cytokines, especially impairment
of adiponectin synthesis, leading to IR. IR enhances hepcidin production through glucose, insulin and
neoglucogenesis. This contributes to decreased hepatic iron excess, which could explain why hepatic
iron excess is frequent in patients who are overweight and rare in those who are obese.
Figure 1. Schematic hypothesis for the development of DIOS. 51
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015
