Original article
Pancreas, biliary tract, and liver
Iron Deficiency in Patients With Nonalcoholic Fatty Liver Disease Is Associated With Obesity, Female Gender, and Low Serum Hepcidin

https://doi.org/10.1016/j.cgh.2013.11.017Get rights and content

Background & Aims

Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines interleukin (IL) 6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin, and IL6 and IL1β, and other risk factors in patients with nonalcoholic fatty liver disease (NAFLD) with iron deficiency.

Methods

We collected data on 675 adult subjects (>18 years old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation <20% were categorized as iron deficient, whereas those with transferrin saturation ≥20% were classified as iron normal. We assessed clinical, demographic, anthropometric, laboratory, dietary, and histologic data from patients, and serum levels of hepcidin and cytokines IL6 and IL1β. Univariate and multivariate analysis were used to identify risk factors for iron deficiency.

Results

One-third of patients (231 of 675; 34%) were iron deficient. Obesity, diabetes, and metabolic syndrome were more common in subjects with iron deficiency (P < .01), compared with those that were iron normal. Serum levels of hepcidin were significantly lower in subjects with iron deficiency (61 ± 45 vs 81 ± 51 ng/mL; P < .0001). Iron deficiency was significantly associated with female gender, obesity, increased body mass index and waist circumference, presence of diabetes, lower alcohol consumption, black or American Indian/Alaska Native race (P ≤ .018), and increased levels of IL6 and IL1β (6.6 vs 4.8 for iron normal, P ≤ .0001; and 0.45 vs 0.32 for iron normal, P ≤ .005).

Conclusions

Iron deficiency is prevalent in patients with NAFLD and associated with female gender, increased body mass index, and nonwhite race. Serum levels of hepcidin were lower in iron-deficient subjects, reflecting an appropriate physiologic response to decreased circulating levels of iron, rather than a primary cause of iron deficiency in the setting of obesity and NAFLD.

Section snippets

Subjects

A total of 675 adult (age >18 years) subjects enrolled in NASH Clinical Research Network (CRN) studies between October 2004 and February 2008, with biopsy-proved NAFLD (defined as >5% steatosis) and serum iron studies within 6 months of the liver biopsy were studied. The NASH CRN Database and PIVENS Trial inclusion/exclusion criteria have been reported elsewhere.15, 16 Demographic information including age, gender, ethnicity, and race and a detailed medical history including comorbidities, such

Patient Characteristics

A total of 675 subjects (mean age, 48 ± 12 years) with biopsy-proved NAFLD (defined as >5% steatosis) and serum iron assessments within 6 months of their liver biopsy were evaluated in the present study. A total of 34% (231 subjects) were ID and 66% (444 subjects) were iron normal (TS ≥20%). Overall, most subjects in this study cohort were white (84%), obese (70%), and female (63%). Patient characteristics including clinical, demographic, racial, and specific dietary/behavioral factors thought

Discussion

ID is common in obese children and adults; the cause of this association is not entirely clear and has been linked to several factors.2, 3, 4, 5, 6, 7 In the present study we found that one-third of adult NAFLD subjects were ID as defined by TS <20%, and that female gender, obesity (BMI ≥30), type 2 diabetes, and MS were more common in this cohort. We also found that alcohol consumption is protective against ID, consistent with our previous data from a population-based study.22 Alcohol has been

Acknowledgments

The authors acknowledge the support of the BRI Genotyping Core facility. They also thank Laura Wilson and Patricia Belt for assistance in preparation of the data. They thank Dr Mark Westerman at Intrinsic Life Sciences for helpful discussions.

A list of the members of the Nonalcoholic Steatohepatitis Clinical Research Network can be found in the Appendix to this article.

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    Conflicts of interest The authors disclose no conflicts.

    Funding The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, and U01DK061713) and the National Institute of Child Health and Human Development. Several clinical centers use support from the National Center for Advancing Translational Sciences in conduct of NASH CRN Studies (grants UL1TR000439, UL1TR000077, UL1TR000436, UL1TR000150, UL1TR000424, UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004, UL1TR000423, UL1TR000058, UL1TR000067, and UL1TR000454). This work was supported in part by the Intramural Research Program of the National Cancer Institute.

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