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, Srinivasan Dasarathy, Arthur J. McCullough, Mangesh Pagadala, Rish Pai & 89 others Ruth Sargent, Manal F. Abdelmalek, Mustafa Bashir, Stephanie Buie, Naga Chalasani, Oscar Cummings, Samer Gawrieh, Marwan Ghabril, Dawn Piercy, Naga Chalasani, Kumar Sandrasegaran, Raj Vuppalanchi, 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, Ryan Gill, Bilal Hameed, Claudia Ramos, Norah Terrault, 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, Jeanne M. Clark, 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, Katherine Yates

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)127-131.e2
JournalClinical Gastroenterology and Hepatology
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Mallory Bodies
Hormones
Inflammation
Physiological Stress
Hepatocytes
Logistic Models
Liver
Hormone Replacement Therapy
Wounds and Injuries
Gonadal Steroid Hormones
Oral Contraceptives
Menopause
Non-alcoholic Fatty Liver Disease

Keywords

  • Fibrosis
  • Gender Differences
  • Risk Factor Analysis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

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

In: Clinical Gastroenterology and Hepatology, Vol. 15, No. 1, 01.01.2017, p. 127-131.e2.

Research output: Contribution to journalArticle

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, Dasarathy, S, McCullough, AJ, Pagadala, M, Pai, R, Sargent, R, Abdelmalek, MF, Bashir, M, Buie, S, Chalasani, N, Cummings, O, Gawrieh, S, Ghabril, M, Piercy, D, Chalasani, N, Sandrasegaran, K, Vuppalanchi, R, 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, Gill, R, Hameed, B, Ramos, C, Terrault, N, 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, Clark, JM, Donithan, M, Hallinan, E, Isaacson, M, May, KP, Miriel, L, Sternberg, A, Tonascia, J, Ünalp-Arida, A, Van Natta, M, Vaughn, I, Wilson, L & Yates, K 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
Yang, Ju Dong ; Abdelmalek, Manal F. ; Guy, Cynthia D. ; Gill, Ryan M. ; Lavine, Joel E. ; Yates, Katherine ; Klair, Jagpal ; Terrault, Norah A. ; Clark, Jeanne M. ; Unalp-Arida, Aynur ; Diehl, Anna Mae ; Suzuki, Ayako ; Dasarathy, Srinivasan ; Dasarathy, Jaividhya ; Hawkins, Carol ; McCullough, Arthur J. ; Dasarathy, Srinivasan ; McCullough, Arthur J. ; Pagadala, Mangesh ; Pai, Rish ; Sargent, Ruth ; Abdelmalek, Manal F. ; Bashir, Mustafa ; Buie, Stephanie ; Chalasani, Naga ; Cummings, Oscar ; Gawrieh, Samer ; Ghabril, Marwan ; Piercy, Dawn ; Chalasani, Naga ; Sandrasegaran, Kumar ; Vuppalanchi, Raj ; Ghabril, Marwan ; Marri, Smitha ; Ragozzino, Linda ; Sandrasegaran, Kumar ; Vuppalanchi, Raj ; King, Debra ; Osmack, Pat ; Siegner, Joan ; Stewart, Susan ; Neuschwander-Tetri, Brent A. ; Torretta, Susan ; Ang, Brandon ; Behling, Cynthia ; Bhatt, Archana ; Loomba, Rohit ; Middleton, Michael ; Patton, Heather ; Sirlin, Claude ; Aouizerat, Bradley ; Bass, Nathan M. ; Brandman, Danielle ; Ferrell, Linda D. ; Gill, Ryan ; Hameed, Bilal ; Ramos, Claudia ; Terrault, Norah ; Ungermann, Ashley ; Atla, Pradeep ; Croft, Brandon ; Garcia, Rebekah ; Garcia, Sonia ; Sheikh, Muhammad ; Singh, Mandeep ; Boyett, Sherry ; Carucci, Laura ; Contos, Melissa J. ; Kraft, Kenneth ; Luketic, Velimir A C ; Puri, Puneet ; Sanyal, Arun J. ; Schlosser, Jolene ; Siddiqui, Mohhamad S. ; Wolford, Ben ; Ackermann, Sarah ; Cooney, Shannon ; Coy, David ; Gelinas, Katie ; Kowdley, Kris V. ; Lee, Maximillian ; Pierce, Tracey ; Mooney, Jody ; Nelson, James E. ; Shaw, Cheryl ; Siddique, Asma ; Wang, Chia ; Brunt, Elizabeth M. ; Fowler, Kathryn ; Kleiner, David E. ; Grave, Gilman D. ; Doo, Edward C. ; Hoofnagle, Jay H. ; Robuck, Patricia R. ; Sherker, Averell ; Belt, Patricia ; Clark, Jeanne M. ; Donithan, Michele ; Hallinan, Erin ; Isaacson, Milana ; May, Kevin P. ; Miriel, Laura ; Sternberg, Alice ; Tonascia, James ; Ünalp-Arida, Aynur ; Van Natta, Mark ; Vaughn, Ivana ; Wilson, Laura ; Yates, Katherine. / Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis. In: Clinical Gastroenterology and Hepatology. 2017 ; Vol. 15, No. 1. pp. 127-131.e2.
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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",
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language = "English (US)",
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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 - Dasarathy, Srinivasan

AU - McCullough, Arthur J.

AU - Pagadala, Mangesh

AU - Pai, Rish

AU - Sargent, Ruth

AU - Abdelmalek, Manal F.

AU - Bashir, Mustafa

AU - Buie, Stephanie

AU - Chalasani, Naga

AU - Cummings, Oscar

AU - Gawrieh, Samer

AU - Ghabril, Marwan

AU - Piercy, Dawn

AU - Chalasani, Naga

AU - Sandrasegaran, Kumar

AU - Vuppalanchi, Raj

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 - Gill, Ryan

AU - Hameed, Bilal

AU - Ramos, Claudia

AU - Terrault, Norah

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 - Clark, Jeanne M.

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

AU - Yates, Katherine

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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U2 - 10.1016/j.cgh.2016.07.034

DO - 10.1016/j.cgh.2016.07.034

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SP - 127-131.e2

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

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