Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis

Ju Dong Yang; Manal F. Abdelmalek; Cynthia D. Guy; Ryan M. Gill; Joel E. Lavine; Katherine Yates; Jagpal Klair; Norah A. Terrault; Jeanne M. Clark; Aynur Unalp-Arida; Anna Mae Diehl; Ayako Suzuki; Srinivasan Dasarathy; Jaividhya Dasarathy; Carol Hawkins; Arthur J. McCullough; Mangesh Pagadala; Rish Pai; Ruth Sargent; Mustafa Bashir; Stephanie Buie; Christopher Kigongo; Yi Ping Pan; Dawn Piercy; Naga Chalasani; Oscar W. Cummings; Samer Gawrieh; Marwan Ghabril; Smitha Marri; Linda Ragozzino; Kumar Sandrasegaran; Raj Vuppalanchi; Debra King; Pat Osmack; Joan Siegner; Susan Stewart; Brent A. Neuschwander-Tetri; Susan Torretta; Brandon Ang; Cynthia Behling; Archana Bhatt; Rohit Loomba; Michael Middleton; Heather Patton; Claude Sirlin; Bradley Aouizerat; Nathan M. Bass; Danielle Brandman; Linda D. Ferrell; Bilal Hameed; Claudia Ramos; Ashley Ungermann; Pradeep Atla; Brandon Croft; Rebekah Garcia; Sonia Garcia; Muhammad Sheikh; Mandeep Singh; Sherry Boyett; Laura Carucci; Melissa J. Contos; Kenneth Kraft; Velimir A.C. Luketic; Puneet Puri; Arun J. Sanyal; Jolene Schlosser; Mohhamad S. Siddiqui; Ben Wolford; Sarah Ackermann; Shannon Cooney; David Coy; Katie Gelinas; Kris V. Kowdley; Maximillian Lee; Tracey Pierce; Jody Mooney; James E. Nelson; Cheryl Shaw; Asma Siddique; 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; Michele Donithan; Erin Hallinan; Milana Isaacson; Kevin P. May; Laura Miriel; Alice Sternberg; James Tonascia; Aynur Ünalp-Arida; Mark Van Natta; Ivana Vaughn; Laura Wilson

doi:10.1016/j.cgh.2016.07.034

Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis

Ju Dong Yang, Manal F. Abdelmalek, Cynthia D. Guy, Ryan M. Gill, Joel E. Lavine, Katherine Yates, Jagpal Klair, Norah A. Terrault, Jeanne M. Clark, Aynur Unalp-Arida, Anna Mae Diehl, Ayako Suzuki, Srinivasan Dasarathy, Jaividhya Dasarathy, Carol Hawkins, Arthur J. McCullough, Mangesh Pagadala, Rish Pai, Ruth Sargent, Mustafa BashirStephanie Buie, Christopher Kigongo, Yi Ping Pan, Dawn Piercy, Naga Chalasani, Oscar W. Cummings, Samer Gawrieh, Marwan Ghabril, Smitha Marri, Linda Ragozzino, Kumar Sandrasegaran, Raj Vuppalanchi, Debra King, Pat Osmack, Joan Siegner, Susan Stewart, Brent A. Neuschwander-Tetri, Susan Torretta, Brandon Ang, Cynthia Behling, Archana Bhatt, Rohit Loomba, Michael Middleton, Heather Patton, Claude Sirlin, Bradley Aouizerat, Nathan M. Bass, Danielle Brandman, Linda D. Ferrell, Bilal Hameed, Claudia Ramos, Ashley Ungermann, Pradeep Atla, Brandon Croft, Rebekah Garcia, Sonia Garcia, Muhammad Sheikh, Mandeep Singh, Sherry Boyett, Laura Carucci, Melissa J. Contos, Kenneth Kraft, Velimir A.C. Luketic, Puneet Puri, Arun J. Sanyal, Jolene Schlosser, Mohhamad S. Siddiqui, Ben Wolford, Sarah Ackermann, Shannon Cooney, David Coy, Katie Gelinas, Kris V. Kowdley, Maximillian Lee, Tracey Pierce, Jody Mooney, James E. Nelson, Cheryl Shaw, Asma Siddique, 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, Michele Donithan, Erin Hallinan, Milana Isaacson, Kevin P. May, Laura Miriel, Alice Sternberg, James Tonascia, Aynur Ünalp-Arida, Mark Van Natta, Ivana Vaughn, Laura Wilson

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

Background & Aims Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. Methods We collected data from 3 large U.S. studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress. Results Premenopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than postmenopausal women (P <.01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in premenopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in postmenopausal women (P <.05). Conclusions Being a premenopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress.

Original language	English (US)
Pages (from-to)	127-131.e2
Journal	Clinical Gastroenterology and Hepatology
Volume	15
Issue number	1
DOIs	https://doi.org/10.1016/j.cgh.2016.07.034
State	Published - Jan 1 2017

Keywords

Fibrosis
Gender Differences
Risk Factor Analysis

ASJC Scopus subject areas

Hepatology
Gastroenterology

Access to Document

10.1016/j.cgh.2016.07.034

Cite this

Yang, J. D., Abdelmalek, M. F., Guy, C. D., Gill, R. M., Lavine, J. E., Yates, K., Klair, J., Terrault, N. A., Clark, J. M., Unalp-Arida, A., Diehl, A. M., Suzuki, A., Dasarathy, S., Dasarathy, J., Hawkins, C., McCullough, A. J., Pagadala, M., Pai, R., Sargent, R., ... Wilson, L. (2017). Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis. Clinical Gastroenterology and Hepatology, 15(1), 127-131.e2. https://doi.org/10.1016/j.cgh.2016.07.034

Yang, JD, Abdelmalek, MF, Guy, CD, Gill, RM, Lavine, JE, Yates, K, Klair, J, Terrault, NA, Clark, JM, Unalp-Arida, A, Diehl, AM, Suzuki, A, Dasarathy, S, Dasarathy, J, Hawkins, C, McCullough, AJ, Pagadala, M, Pai, R, Sargent, R, Bashir, M, Buie, S, Kigongo, C, Pan, YP, Piercy, D, Chalasani, N, Cummings, OW, Gawrieh, S, Ghabril, M, Marri, S, Ragozzino, L, Sandrasegaran, K, Vuppalanchi, R, King, D, Osmack, P, Siegner, J, Stewart, S, Neuschwander-Tetri, BA, Torretta, S, Ang, B, Behling, C, Bhatt, A, Loomba, R, Middleton, M, Patton, H, Sirlin, C, Aouizerat, B, Bass, NM, Brandman, D, Ferrell, LD, Hameed, B, Ramos, C, Ungermann, A, Atla, P, Croft, B, Garcia, R, Garcia, S, Sheikh, M, Singh, M, Boyett, S, Carucci, L, Contos, MJ, Kraft, K, Luketic, VAC, Puri, P, Sanyal, AJ, Schlosser, J, Siddiqui, MS, Wolford, B, Ackermann, S, Cooney, S, Coy, D, Gelinas, K, Kowdley, KV, Lee, M, Pierce, T, Mooney, J, Nelson, JE, Shaw, C, Siddique, A, Wang, C, Brunt, EM, Fowler, K, Kleiner, DE, Grave, GD, Doo, EC, Hoofnagle, JH, Robuck, PR, Sherker, A, Belt, P, Donithan, M, Hallinan, E, Isaacson, M, May, KP, Miriel, L, Sternberg, A, Tonascia, J, Ünalp-Arida, A, Van Natta, M, Vaughn, I & Wilson, L 2017, 'Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis', Clinical Gastroenterology and Hepatology, vol. 15, no. 1, pp. 127-131.e2. https://doi.org/10.1016/j.cgh.2016.07.034

@article{0cdea4cf74394391a2fc96936b62343d,

title = "Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis",

abstract = "Background & Aims Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. Methods We collected data from 3 large U.S. studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress. Results Premenopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than postmenopausal women (P <.01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in premenopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in postmenopausal women (P <.05). Conclusions Being a premenopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress.",

keywords = "Fibrosis, Gender Differences, Risk Factor Analysis",

author = "Yang, {Ju Dong} and Abdelmalek, {Manal F.} and Guy, {Cynthia D.} and Gill, {Ryan M.} and Lavine, {Joel E.} and Katherine Yates and Jagpal Klair and Terrault, {Norah A.} and Clark, {Jeanne M.} and Aynur Unalp-Arida and Diehl, {Anna Mae} and Ayako Suzuki and Srinivasan Dasarathy and Jaividhya Dasarathy and Carol Hawkins and McCullough, {Arthur J.} and Mangesh Pagadala and Rish Pai and Ruth Sargent and Mustafa Bashir and Stephanie Buie and Christopher Kigongo and Pan, {Yi Ping} and Dawn Piercy and Naga Chalasani and Cummings, {Oscar W.} and Samer Gawrieh and Marwan Ghabril and Smitha Marri and Linda Ragozzino and Kumar Sandrasegaran and Raj Vuppalanchi and Debra King and Pat Osmack and Joan Siegner and Susan Stewart and Neuschwander-Tetri, {Brent A.} and Susan Torretta and Brandon Ang and Cynthia Behling and Archana Bhatt and Rohit Loomba and Michael Middleton and Heather Patton and Claude Sirlin and Bradley Aouizerat and Bass, {Nathan M.} and Danielle Brandman and Ferrell, {Linda D.} and Bilal Hameed and Claudia Ramos and Ashley Ungermann and Pradeep Atla and Brandon Croft and Rebekah Garcia and Sonia Garcia and Muhammad Sheikh and Mandeep Singh and Sherry Boyett and Laura Carucci and Contos, {Melissa J.} and Kenneth Kraft and Luketic, {Velimir A.C.} and Puneet Puri and Sanyal, {Arun J.} and Jolene Schlosser and Siddiqui, {Mohhamad S.} and Ben Wolford and Sarah Ackermann and Shannon Cooney and David Coy and Katie Gelinas and Kowdley, {Kris V.} and Maximillian Lee and Tracey Pierce and Jody Mooney and Nelson, {James E.} and Cheryl Shaw and Asma Siddique 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 Michele Donithan and Erin Hallinan and Milana Isaacson and May, {Kevin P.} and Laura Miriel and Alice Sternberg and James Tonascia and Aynur {\"U}nalp-Arida and {Van Natta}, Mark and Ivana Vaughn and Laura Wilson",

note = "Publisher Copyright: {\textcopyright} 2017 AGA Institute",

year = "2017",

month = jan,

day = "1",

doi = "10.1016/j.cgh.2016.07.034",

language = "English (US)",

volume = "15",

pages = "127--131.e2",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

publisher = "W.B. Saunders Ltd",

number = "1",

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TY - JOUR

T1 - Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis

AU - Yang, Ju Dong

AU - Abdelmalek, Manal F.

AU - Guy, Cynthia D.

AU - Gill, Ryan M.

AU - Lavine, Joel E.

AU - Yates, Katherine

AU - Klair, Jagpal

AU - Terrault, Norah A.

AU - Clark, Jeanne M.

AU - Unalp-Arida, Aynur

AU - Diehl, Anna Mae

AU - Suzuki, Ayako

AU - Dasarathy, Srinivasan

AU - Dasarathy, Jaividhya

AU - Hawkins, Carol

AU - McCullough, Arthur J.

AU - Pagadala, Mangesh

AU - Pai, Rish

AU - Sargent, Ruth

AU - Bashir, Mustafa

AU - Buie, Stephanie

AU - Kigongo, Christopher

AU - Pan, Yi Ping

AU - Piercy, Dawn

AU - Chalasani, Naga

AU - Cummings, Oscar W.

AU - Gawrieh, Samer

AU - Ghabril, Marwan

AU - Marri, Smitha

AU - Ragozzino, Linda

AU - Sandrasegaran, Kumar

AU - Vuppalanchi, Raj

AU - King, Debra

AU - Osmack, Pat

AU - Siegner, Joan

AU - Stewart, Susan

AU - Neuschwander-Tetri, Brent A.

AU - Torretta, Susan

AU - Ang, Brandon

AU - Behling, Cynthia

AU - Bhatt, Archana

AU - Loomba, Rohit

AU - Middleton, Michael

AU - Patton, Heather

AU - Sirlin, Claude

AU - Aouizerat, Bradley

AU - Bass, Nathan M.

AU - Brandman, Danielle

AU - Ferrell, Linda D.

AU - Hameed, Bilal

AU - Ramos, Claudia

AU - Ungermann, Ashley

AU - Atla, Pradeep

AU - Croft, Brandon

AU - Garcia, Rebekah

AU - Garcia, Sonia

AU - Sheikh, Muhammad

AU - Singh, Mandeep

AU - Boyett, Sherry

AU - Carucci, Laura

AU - Contos, Melissa J.

AU - Kraft, Kenneth

AU - Luketic, Velimir A.C.

AU - Puri, Puneet

AU - Sanyal, Arun J.

AU - Schlosser, Jolene

AU - Siddiqui, Mohhamad S.

AU - Wolford, Ben

AU - Ackermann, Sarah

AU - Cooney, Shannon

AU - Coy, David

AU - Gelinas, Katie

AU - Kowdley, Kris V.

AU - Lee, Maximillian

AU - Pierce, Tracey

AU - Mooney, Jody

AU - Nelson, James E.

AU - Shaw, Cheryl

AU - Siddique, Asma

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 - Donithan, Michele

AU - Hallinan, Erin

AU - Isaacson, Milana

AU - May, Kevin P.

AU - Miriel, Laura

AU - Sternberg, Alice

AU - Tonascia, James

AU - Ünalp-Arida, Aynur

AU - Van Natta, Mark

AU - Vaughn, Ivana

AU - Wilson, Laura

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background & Aims Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. Methods We collected data from 3 large U.S. studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress. Results Premenopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than postmenopausal women (P <.01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in premenopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in postmenopausal women (P <.05). Conclusions Being a premenopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress.

AB - Background & Aims Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. Methods We collected data from 3 large U.S. studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress. Results Premenopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than postmenopausal women (P <.01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in premenopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in postmenopausal women (P <.05). Conclusions Being a premenopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress.

KW - Fibrosis

KW - Gender Differences

KW - Risk Factor Analysis

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