Am J Gastroenterol. 2007 Mar 27; [Epub ahead of print]Iron Depletion
by Phlebotomy Improves Insulin Resistance in Patients With
Nonalcoholic Fatty Liver Disease and Hyperferritinemia: Evidence from
a Case-Control Study.Valenti L, Fracanzani AL, Dongiovanni P,
Bugianesi E, Marchesini G, Manzini P, Vanni E, Fargion S.
Department of Internal Medicine, Universita' di Milano, Ospedale
Policlinico Mangiagalli Regina Elena IRCCS, Milano, Italy.

OBJECTIVES: Hyperferritinemia is frequently observed in nonalcoholic
fatty liver disease (NAFLD), the hepatic manifestation of the
metabolic syndrome characterized by hepatic insulin resistance and
considered high cardiovascular risk. Iron depletion by phlebotomy has
been reported to decrease insulin resistance in NAFLD in small,
uncontrolled studies. Aims of this study were to define the
relationship between ferritin and iron stores in patients with NAFLD,
the effect of iron depletion on insulin resistance, and whether basal
ferritin levels influence treatment outcome. METHODS: Subjects were
included if ferritin and/or ALT were persistently elevated after 4
months of standard therapy. Sixty-four phlebotomized subjects were
matched 1:1 for age, sex, ferritin, obesity, and ALT levels with
patients who underwent lifestyle modifications only. Insulin
resistance was evaluated by insulin levels, determined by RIA and the
HOMA-R index, at baseline and after 8 months. RESULTS: Baseline
ferritin levels were associated with body iron stores (P < 0.0001).
Iron depletion produced a significantly larger decrease in insulin
resistance (P= 0.0016 for insulin, P= 0.0042 for HOMA-R) compared with
nutritional counseling alone, independent of changes in BMI, baseline
HOMA-R, and the presence of the metabolic syndrome. Iron depletion was
more effective in reducing HOMA-R in patients in the top two tertiles
of ferritin concentrations (P < 0.05 vs controls), and in carriers of
the mutations in the HFE gene of hereditary hemochromatosis (P < 0.05
vs noncarriers). CONCLUSIONS: Given that phlebotomy reduces insulin
resistance, which is associated with liver tissue damage, future
studies should evaluate the effect of iron depletion on liver
histology and cardiovascular end points.

PMID: 17391316 [PubMed - as supplied by publisher]

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