Bloodletting In NAFLD...

Quote:

American Journal of Clinical Nutrition, Vol. 87, No. 5, 1374-1383, May
2008
© 2008 American Society for Nutrition

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ORIGINAL RESEARCH COMMUNICATION

Pathways underlying iron accumulation in human nonalcoholic fatty
liver disease1,2,3
Elmar Aigner, Igor Theurl, Milan Theurl, Dieter Lederer, Heike Haufe,
Otto Dietze, Michael Strasser, Christian Datz and Guenter Weiss
1 From the Department of Internal Medicine, General Hospital
Oberndorf, Oberndorf, Austria (EA, DL, and CD); the Department of
General Internal Medicine, Department of Immunology and Infectious
Diseases, Medical University of Innsbruck, Austria (IT, MT, and GW);
the Department of Pathology (HH and OD) and the First Department of
Medicine (MS), Paracelsus Private Medical University Salzburg,
Austria

Background: Mild iron overload is frequently observed in nonalcoholic
fatty liver disease (NAFLD).

Objective: We aimed to study putative pathways underlying iron
accumulation in NAFLD.

Design: Hepatic and duodenal expression of critical iron molecules in
NAFLD patients with (n = 32) and without (n = 29) iron overload,
hereditary hemochromatosis (n = 10), and controls (n = 20) were
investigated. Phlebotomy treatment was performed in 14 NAFLD
patients.

Results: The hepatic expressions of the iron-export protein
ferroportin-1 (FP-1) and of the iron-sensing molecule hemojuvelin
(HJV) were significantly lower in NAFLD patients. The mRNA expression
of the iron-regulatory peptide hepcidin was increased in NAFLD
patients with iron overload, which was paralleled by low duodenal FP-1
expression. Hepatic mRNA and serum protein concentrations of tumor
necrosis factor- (TNF-) were increased in NAFLD patients and were
inversely correlated with both liver FP-1 and HJV mRNA and positively
associated with body mass index and hepatic hepcidin mRNA.
Accordingly, TNF- inhibited the FP-1 and HJV mRNA formation in HepG2
cells. Phlebotomy treatment of NALFD patients reduced serum ferritin,
transferrin saturation, and TNF- concentrations and improved liver
function tests.

Conclusions: Iron accumulation in NAFLD may result from an impaired
iron export due to down-regulation of FP1 and ineffective hepatic iron
sensing, as indicated by low HJV expression. TNF- appears to play a
role in exerting these regulatory changes. Increased hepcidin
formation in iron-overloaded NAFLD patients, however, results in
decreased duodenal FP-1 expression, whereas a reduction in liver FP-1
may perpetuate hepatic iron retention. Phlebotomy offers a safe and
efficient therapy for these metabolic disturbances.

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