Page 50 - EASL POSTGRADUATE COURSE
P. 50
NAFLD and interactions with insulin resistance
DYSMETABOLIC HYPERFERRITINEMIA
Yves Deugnier, Edouard Bardou-Jacquet, Carolie Jézéquel and Fabrice Lainé
University Hospital, Rennes 1 University, INSERM CIC 1414;
Liver Unit, Pontchaillou Hospital, 35033 Rennes, France
E-mail: yves.deugnier@univ-rennes1.fr
Take home messages
Dysmetabolic Iron Overload Syndrome (DIOS) is:
• defined by hyperferritinemia (500-1500 µg/l) with normal transferrin saturation and mild hepatic
iron excess (50-150 µmol/g) in the setting of various features of the MetS;
• diagnosed by magnetic resonance imaging or liver biopsy;
• associated with non-alcoholic fatty liver disease in 50% of cases and with an increased risk of diabetes,
cardiovascular complications, and cancer;
• easily treated by phlebotomies, but not by lifestyle modifications alone.
Introduction [1-3]
Mild hyperferritinemia is frequent in patients with metabolic abnormalities and related cardiovascular and
hepatic complications. It correlates with the degree of IR as measured by the euglycemic hyperinsulinemic
clamp, with the number of components of the MetS and with the decrease in serum adiponectin levels.
Moreover, it is predictive of the onset of T2DM. It raises diagnostic, pathophysiologic and therapeutic
issues, especially when it accounts for elevated body iron stores, coined as the dysmetabolic iron overload
syndrome (DIOS).
Diagnosis
Three conditions frequently associated with MetS, chronic inflammation, excessive alcohol consumption
and cell necrosis, may increase serum ferritin levels in the absence of elevated body iron stores. This
must be discussed first.
It is then necessary to check transferrin saturation at least twice because of the frequency of false positive
results:
• Transferrin saturation elevated: the diagnosis of HFE hemochromatosis is a possibility and HFE
genotyping should be performed.
• Transferrin saturation NOT elevated: assess hepatic iron concentration (HIC) (normal HIC =
36 µmol/g dry weight) to determine whether body iron stores are elevated or not.
o HIC is assessed in the following ways:
§ Liver biopsy: if indicated for the assessment of associated NAFLD.
§ MRI: when the device is correctly calibrated, MRI allows reliable identification and
quantification of HIC in a wide range from 60 to 300 µmol/g dry weight. This technique also
permits the detection of iron deposition in the spleen.
50 Postgraduate Course Syllabus • Metabolic Liver Disease
DYSMETABOLIC HYPERFERRITINEMIA
Yves Deugnier, Edouard Bardou-Jacquet, Carolie Jézéquel and Fabrice Lainé
University Hospital, Rennes 1 University, INSERM CIC 1414;
Liver Unit, Pontchaillou Hospital, 35033 Rennes, France
E-mail: yves.deugnier@univ-rennes1.fr
Take home messages
Dysmetabolic Iron Overload Syndrome (DIOS) is:
• defined by hyperferritinemia (500-1500 µg/l) with normal transferrin saturation and mild hepatic
iron excess (50-150 µmol/g) in the setting of various features of the MetS;
• diagnosed by magnetic resonance imaging or liver biopsy;
• associated with non-alcoholic fatty liver disease in 50% of cases and with an increased risk of diabetes,
cardiovascular complications, and cancer;
• easily treated by phlebotomies, but not by lifestyle modifications alone.
Introduction [1-3]
Mild hyperferritinemia is frequent in patients with metabolic abnormalities and related cardiovascular and
hepatic complications. It correlates with the degree of IR as measured by the euglycemic hyperinsulinemic
clamp, with the number of components of the MetS and with the decrease in serum adiponectin levels.
Moreover, it is predictive of the onset of T2DM. It raises diagnostic, pathophysiologic and therapeutic
issues, especially when it accounts for elevated body iron stores, coined as the dysmetabolic iron overload
syndrome (DIOS).
Diagnosis
Three conditions frequently associated with MetS, chronic inflammation, excessive alcohol consumption
and cell necrosis, may increase serum ferritin levels in the absence of elevated body iron stores. This
must be discussed first.
It is then necessary to check transferrin saturation at least twice because of the frequency of false positive
results:
• Transferrin saturation elevated: the diagnosis of HFE hemochromatosis is a possibility and HFE
genotyping should be performed.
• Transferrin saturation NOT elevated: assess hepatic iron concentration (HIC) (normal HIC =
36 µmol/g dry weight) to determine whether body iron stores are elevated or not.
o HIC is assessed in the following ways:
§ Liver biopsy: if indicated for the assessment of associated NAFLD.
§ MRI: when the device is correctly calibrated, MRI allows reliable identification and
quantification of HIC in a wide range from 60 to 300 µmol/g dry weight. This technique also
permits the detection of iron deposition in the spleen.
50 Postgraduate Course Syllabus • Metabolic Liver Disease
