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 Zein; Kimberlee 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

doi:10.1016/j.cgh.2013.11.017

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 journal › Article › peer-review

19 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 language	English (US)
Pages (from-to)	1170-1178
Number of pages	9
Journal	Clinical Gastroenterology and Hepatology
Volume	12
Issue number	7
DOIs	https://doi.org/10.1016/j.cgh.2013.11.017
State	Published - Jul 2014

Keywords

BMI
Ferroportin
Inflammation
NAFLD
NASH CRN
Nutrition

ASJC Scopus subject areas

Hepatology
Gastroenterology

Access to Document

10.1016/j.cgh.2013.11.017

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

Siddique, A, Nelson, JE, Aouizerat, B, Yeh, MM, Kowdley, KV, Abrams, SH, Himes, R, Krisnamurthy, R, Maldonado, L, Morris, B, Brandt, P, Dasarathy, S, Dasarathy, J, Hawkins, C, McCullough, AJ, Pagadala, M, Pai, R, Sargent, R, Shah, S, Zein, C, Bernstein, K, Cecil, K, DeVore, S, Kohli, R, Lake, K, Podberesky, D, Slaughter, C, Xanthakos, S, Behr, G, Lavine, JE, Mencin, A, Ovchinsky, N, Reynoso, E, Abdelmalek, MF, Bashir, M, Buie, S, Diehl, AM, Guy, C, Kigongo, C, Pan, YP, Piercy, D, Wagner, M, Alazraki, A, Cleeton, R, Karpen, S, Raviele, N, Vos, M, Byam, E, Chalasani, N, Cummings, OW, Fleming, C, Ghabril, M, Klipsch, A, Marri, S, Molleston, JP, Ragozzino, L, Sandrasegaran, K, Subbarao, G, Vuppalanchi, R, Pfeifer, K, Scheimann, A, Torbenson, M, Arnon, R, Boyd, M, Amsden, K, Fishbein, MH, Kirwan, E, Mohammad, S, Quinn, A, Rigsby, C, Whitington, PF, Barlow, S, Derdoy, J, Jain, A, King, D, Osmack, P, Siegner, J, Stewart, S, Neuschwander-Tetri, BA, Romo, D, Ang, B, Arroyo, S, Behling, C, Bhatt, A, Collins, J, Doycheva, I, Durelle, J, Hassanein, T, Loomba, R, Middleton, M, Newton, K, Nguyen, P, Noureddin, M, Paiz, M, Patton, H, Schwimmer, JB, Sirlin, C, Ugalde-Nicalo, P, Bass, NM, Brandman, D, Ferrell, LD, Fleck, S, Gill, R, Hameed, B, Ko, A, Langlois, C, Perito, ER, Qayyum, A, Rosenthal, P, Terrault, N, Tsai, P, Atla, P, Hurtado, C, Garcia, R, Garcia, S, Sheikh, M, Singh, M, Cooper, K, Horslen, S, Hsu, E, Murray, K, Otto, R, Rich, D, Yeh, M, Young, M, Boyett, S, Carucci, L, Contos, MJ, Fuchs, M, Jones, A, Kraft, K, Luketic, VAC, Noble, K, Puri, P, Sandhu, B, Sanyal, AJ, Sargeant, C, Schlosser, J, Siddiqui, MS, Wolford, B, White, M, Ackermann, S, Cooney, S, Coy, D, Gelinas, K, Lee, M, Pierce, T, Mooney, J, Siekas, L, Shaw, C, Wang, C, Brunt, EM, Fowler, K, Kleiner, DE, Grave, GD, Doo, EC, Hoofnagle, JH, Robuck, PR, Sherker, A, Belt, P, Clark, JM, Corless, E, Donithan, M, Isaacson, M, May, KP, Miriel, L, Sternberg, A, Tonascia, J, Aynur ünalp-Arida, Ü-A, Natta, MV, Vaughn, I, Wilson, L & 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, vol. 12, no. 7, pp. 1170-1178. https://doi.org/10.1016/j.cgh.2013.11.017

@article{cd84a81929914a639ab633963e208102,

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

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.",

keywords = "BMI, Ferroportin, Inflammation, NAFLD, NASH CRN, Nutrition",

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

note = "Funding Information: 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 . ",

year = "2014",

month = jul,

doi = "10.1016/j.cgh.2013.11.017",

language = "English (US)",

volume = "12",

pages = "1170--1178",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

publisher = "W.B. Saunders Ltd",

number = "7",

}

TY - JOUR

T1 - Iron deficiency in patients with nonalcoholic fatty liver disease is associated with obesity, female gender, and low serum hepcidin

AU - Siddique, Asma

AU - Nelson, James E.

AU - Aouizerat, Bradley

AU - Yeh, Matthew M.

AU - Kowdley, Kris V.

AU - Abrams, Stephanie H.

AU - Himes, Ryan

AU - Krisnamurthy, Rajesh

AU - Maldonado, Leanel

AU - Morris, Beverly

AU - Brandt, Patricia

AU - Dasarathy, Srinivasan

AU - Dasarathy, Jaividhya

AU - Hawkins, Carol

AU - McCullough, Arthur J.

AU - Pagadala, Mangesh

AU - Pai, Rish

AU - Sargent, Ruth

AU - Shah, Shetal

AU - Zein, Claudia

AU - Bernstein, Kimberlee

AU - Cecil, Kim

AU - DeVore, Stephanie

AU - Kohli, Rohit

AU - Lake, Kathleen

AU - Podberesky, Daniel

AU - Slaughter, Crystal

AU - Xanthakos, Stavra

AU - Behr, Gerald

AU - Lavine, Joel E.

AU - Mencin, Ali

AU - Ovchinsky, Nadia

AU - Reynoso, Elena

AU - Abdelmalek, Manal F.

AU - Bashir, Mustafa

AU - Buie, Stephanie

AU - Diehl, Anna Mae

AU - Guy, Cynthia

AU - Kigongo, Christopher

AU - Pan, Yi Ping

AU - Piercy, Dawn

AU - Wagner, Melissa

AU - Alazraki, Adina

AU - Cleeton, Rebecca

AU - Karpen, Saul

AU - Raviele, Nicholas

AU - Vos, Miriam

AU - Byam, Elizabeth

AU - Chalasani, Naga

AU - Cummings, Oscar W.

AU - Fleming, Cynthia

AU - Ghabril, Marwan

AU - Klipsch, Ann

AU - Marri, Smitha

AU - Molleston, Jean P.

AU - Ragozzino, Linda

AU - Sandrasegaran, Kumar

AU - Subbarao, Girish

AU - Vuppalanchi, Raj

AU - Pfeifer, Kimberly

AU - Scheimann, Ann

AU - Torbenson, Michael

AU - Arnon, Ronen

AU - Boyd, Mariel

AU - Amsden, Katie

AU - Fishbein, Mark H.

AU - Kirwan, Elizabeth

AU - Mohammad, Saeed

AU - Quinn, Ann

AU - Rigsby, Cynthia

AU - Whitington, Peter F.

AU - Barlow, Sarah

AU - Derdoy, Jose

AU - Jain, Ajay

AU - King, Debra

AU - Osmack, Pat

AU - Siegner, Joan

AU - Stewart, Susan

AU - Neuschwander-Tetri, Brent A.

AU - Romo, Dana

AU - Ang, Brandon

AU - Arroyo, Sandra

AU - Behling, Cynthia

AU - Bhatt, Archana

AU - Collins, Jennifer

AU - Doycheva, Iliana

AU - Durelle, Janis

AU - Hassanein, Tarek

AU - Loomba, Rohit

AU - Middleton, Michael

AU - Newton, Kimberly

AU - Nguyen, Phirum

AU - Noureddin, Mazen

AU - Paiz, Melissa

AU - Patton, Heather

AU - Schwimmer, Jeffrey B.

AU - Sirlin, Claude

AU - Ugalde-Nicalo, Patricia

AU - Bass, Nathan M.

AU - Brandman, Danielle

AU - Ferrell, Linda D.

AU - Fleck, Shannon

AU - Gill, Ryan

AU - Hameed, Bilal

AU - Ko, Alexander

AU - Langlois, Camille

AU - Perito, Emily Rothbaum

AU - Qayyum, Aliya

AU - Rosenthal, Philip

AU - Terrault, Norah

AU - Tsai, Patrika

AU - Atla, Pradeep

AU - Hurtado, Cathy

AU - Garcia, Rebekah

AU - Garcia, Sonia

AU - Sheikh, Muhammad

AU - Singh, Mandeep

AU - Cooper, Kara

AU - Horslen, Simon

AU - Hsu, Evelyn

AU - Murray, Karen

AU - Otto, Randolph

AU - Rich, Deana

AU - Yeh, Matthew

AU - Young, Melissa

AU - Boyett, Sherry

AU - Carucci, Laura

AU - Contos, Melissa J.

AU - Fuchs, Michael

AU - Jones, Amy

AU - Kraft, Kenneth

AU - Luketic, Velimir A.C.

AU - Noble, Kimberly

AU - Puri, Puneet

AU - Sandhu, Bimalijit

AU - Sanyal, Arun J.

AU - Sargeant, Carol

AU - Schlosser, Jolene

AU - Siddiqui, Mohhamad S.

AU - Wolford, Ben

AU - White, Melanie

AU - Ackermann, Sarah

AU - Cooney, Shannon

AU - Coy, David

AU - Gelinas, Katie

AU - Lee, Maximillian

AU - Pierce, Tracey

AU - Mooney, Jody

AU - Siekas, Lacey

AU - Shaw, Cheryl

AU - Wang, Chia

AU - Brunt, Elizabeth M.

AU - Fowler, Kathryn

AU - Kleiner, David E.

AU - Grave, Gilman D.

AU - Doo, Edward C.

AU - Hoofnagle, Jay H.

AU - Robuck, Patricia R.

AU - Sherker, Averell

AU - Belt, Patricia

AU - Clark, Jeanne M.

AU - Corless, Erin

AU - Donithan, Michele

AU - Isaacson, Milana

AU - May, Kevin P.

AU - Miriel, Laura

AU - Sternberg, Alice

AU - Tonascia, James

AU - Aynur ünalp-Arida, ünalp-Arida

AU - Natta, Mark Van

AU - Vaughn, Ivana

AU - Wilson, Laura

AU - Yates, Katherine

N1 - Funding Information: 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 .

PY - 2014/7

Y1 - 2014/7

N2 - 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.

AB - 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.

KW - BMI

KW - Ferroportin

KW - Inflammation

KW - NAFLD

KW - NASH CRN

KW - Nutrition

UR - http://www.scopus.com/inward/record.url?scp=84902533159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902533159&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2013.11.017

DO - 10.1016/j.cgh.2013.11.017

M3 - Article

C2 - 24269922

AN - SCOPUS:84902533159

VL - 12

SP - 1170

EP - 1178

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 7

ER -

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

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