Ju Dong Yang1, Manal F Abdelmalek2, Cynthia D Guy3, Ryan M Gill4, Joel E Lavine5, Katherine Yates6, Jagpal Klair7, Norah A Terrault8, Jeanne M Clark9, Aynur Unalp-Arida10, Anna Mae Diehl2, Ayako Suzuki11. 1. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota. 2. Gastroenterology and Hepatology, Duke University, Durham, North Carolina. 3. Department of Pathology, Duke University, Durham, North Carolina. 4. Department of Pathology, University of California San Francisco, San Francisco, California. 5. Department of Pediatrics, Columbia University, New York, New York. 6. Nonalcoholic Steatohepatitis Clinical Research Network Data Coordinating Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 7. Division of Gastroenterology and Hepatology, University of Iowa Hospitals and Clinics, Iowa City, Iowa. 8. Division of Gastroenterology, University of California San Francisco, San Francisco, California. 9. Departments of Medicine and Epidemiology, Johns Hopkins University, Baltimore, Maryland. 10. Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. 11. Gastroenterology and Hepatology, Duke University, Durham, North Carolina; Gastroenterology, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas. Electronic address: ayako.suzuki@va.gov.
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.
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.
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