Iron deficiency in patients with nonalcoholic fatty liver disease is associated with obesity, female gender, and low serum hepcidin

Asma Siddique, James E. Nelson, Bradley Aouizerat, Matthew M. Yeh, Kris V. Kowdley, Stephanie H. Abrams, Ryan Himes, Rajesh Krisnamurthy, Leanel Maldonado, Beverly Morris, Patricia Brandt, Srinivasan Dasarathy, Jaividhya Dasarathy, Carol Hawkins, Arthur J. McCullough, Mangesh Pagadala, Rish Pai, Ruth Sargent, Shetal Shah, Claudia ZeinKimberlee Bernstein, Kim Cecil, Stephanie DeVore, Rohit Kohli, Kathleen Lake, Daniel Podberesky, Crystal Slaughter, Stavra Xanthakos, Gerald Behr, Joel E. Lavine, Ali Mencin, Nadia Ovchinsky, Elena Reynoso, Manal F. Abdelmalek, Mustafa Bashir, Stephanie Buie, Anna Mae Diehl, Cynthia Guy, Christopher Kigongo, Yi Ping Pan, Dawn Piercy, Melissa Wagner, Adina Alazraki, Rebecca Cleeton, Saul Karpen, Nicholas Raviele, Miriam Vos, Elizabeth Byam, Naga Chalasani, Oscar W. Cummings, Cynthia Fleming, Marwan Ghabril, Ann Klipsch, Smitha Marri, Jean P. Molleston, Linda Ragozzino, Kumar Sandrasegaran, Girish Subbarao, Raj Vuppalanchi, Kimberly Pfeifer, Ann Scheimann, Michael Torbenson, Ronen Arnon, Mariel Boyd, Katie Amsden, Mark H. Fishbein, Elizabeth Kirwan, Saeed Mohammad, Ann Quinn, Cynthia Rigsby, Peter F. Whitington, Sarah Barlow, Jose Derdoy, Ajay Jain, Debra King, Pat Osmack, Joan Siegner, Susan Stewart, Brent A. Neuschwander-Tetri, Dana Romo, Brandon Ang, Sandra Arroyo, Cynthia Behling, Archana Bhatt, Jennifer Collins, Iliana Doycheva, Janis Durelle, Tarek Hassanein, Rohit Loomba, Michael Middleton, Kimberly Newton, Phirum Nguyen, Mazen Noureddin, Melissa Paiz, Heather Patton, Jeffrey B. Schwimmer, Claude Sirlin, Patricia Ugalde-Nicalo, Nathan M. Bass, Danielle Brandman, Linda D. Ferrell, Shannon Fleck, Ryan Gill, Bilal Hameed, Alexander Ko, Camille Langlois, Emily Rothbaum Perito, Aliya Qayyum, Philip Rosenthal, Norah Terrault, Patrika Tsai, Pradeep Atla, Cathy Hurtado, Rebekah Garcia, Sonia Garcia, Muhammad Sheikh, Mandeep Singh, Kara Cooper, Simon Horslen, Evelyn Hsu, Karen Murray, Randolph Otto, Deana Rich, Matthew Yeh, Melissa Young, Sherry Boyett, Laura Carucci, Melissa J. Contos, Michael Fuchs, Amy Jones, Kenneth Kraft, Velimir A.C. Luketic, Kimberly Noble, Puneet Puri, Bimalijit Sandhu, Arun J. Sanyal, Carol Sargeant, Jolene Schlosser, Mohhamad S. Siddiqui, Ben Wolford, Melanie White, Sarah Ackermann, Shannon Cooney, David Coy, Katie Gelinas, Maximillian Lee, Tracey Pierce, Jody Mooney, Lacey Siekas, Cheryl Shaw, Chia Wang, Elizabeth M. Brunt, Kathryn Fowler, David E. Kleiner, Gilman D. Grave, Edward C. Doo, Jay H. Hoofnagle, Patricia R. Robuck, Averell Sherker, Patricia Belt, Jeanne M. Clark, Erin Corless, Michele Donithan, Milana Isaacson, Kevin P. May, Laura Miriel, Alice Sternberg, James Tonascia, ünalp-Arida Aynur ünalp-Arida, Mark Van Natta, Ivana Vaughn, Laura Wilson, Katherine Yates

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1170-1178
Number of pages9
JournalClinical Gastroenterology and Hepatology
Volume12
Issue number7
DOIs
StatePublished - Jul 2014

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Keywords

  • BMI
  • Ferroportin
  • Inflammation
  • NAFLD
  • NASH CRN
  • Nutrition

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Siddique, A., Nelson, J. E., Aouizerat, B., Yeh, M. M., Kowdley, K. V., Abrams, S. H., Himes, R., Krisnamurthy, R., Maldonado, L., Morris, B., Brandt, P., Dasarathy, S., Dasarathy, J., Hawkins, C., McCullough, A. J., Pagadala, M., Pai, R., Sargent, R., Shah, S., ... Yates, K. (2014). Iron deficiency in patients with nonalcoholic fatty liver disease is associated with obesity, female gender, and low serum hepcidin. Clinical Gastroenterology and Hepatology, 12(7), 1170-1178. https://doi.org/10.1016/j.cgh.2013.11.017