Original Contribution
The American Journal of Gastroenterology (2007) 102, 1251–1258; doi:10.1111/j.1572-0241.2007.01192.x
Iron Depletion by Phlebotomy Improves Insulin Resistance in Patients With Nonalcoholic Fatty Liver Disease and Hyperferritinemia: Evidence from a Case-Control Study
Luca Valenti MD1, Anna Ludovica Fracanzani MD1, Paola Dongiovanni PhD1, Elisabetta Bugianesi MD2, Giulio Marchesini MD3, Paola Manzini MD4, Ester Vanni MD2 and Silvia Fargion MD1
- 1Department of Internal Medicine, Universita' di Milano, Ospedale Policlinico Mangiagalli Regina Elena IRCCS, Milano, Italy
- 2Department of Gastroenterology, Universita' di Torino, Torino, Italy
- 3Unit of Metabolic Diseases, Universita' di Bologna, Bologna, Italy
- 4Blood center, Ospedale San Giovanni Battista, Torino, Italy
Correspondence: Prof Silvia Fargion, Dipartimento di Medicina Interna, UO Medicina Interna IB, Padiglione Granelli, Universita' degli Studi di Milano, Ospedale Policlinico Mangialli e Regina Elena Fondazione IRCCS, Via F Sforza 35, 20122 Milano (MI), Italy.
Received 27 October 2006; Accepted 28 January 2007.
Abstract
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.
