title: Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis.
abstract: Estrogens inhibit stellate cell activation and fibrogenesis. Thus, gender and reproductive states may influence the degree of fibrosis in patients with nonalcoholic steatohepatitis (NASH). To investigate the association between gender, menopause, and the severity of liver fibrosis in patients with NASH, we analyzed 541 adult patients enrolled from our Duke Liver Clinics (n = 338) and the Duke Metabolic and Weight Loss Surgery Program (n = 203) who had a histologic diagnosis of NASH. Multiple ordinal logistic regression models were used to assess the association between gender, menopause, and severity of liver fibrosis. Overall, men, premenopausal, and postmenopausal women composed 35.1%, 28.4%, and 36.5% of the population, respectively. The mean age was 48 years and 22% had advanced fibrosis. After adjusting for covariates (enrolling site, grades of portal inflammation, and hepatocyte ballooning) and potential confounders (race, body mass index, diabetes/prediabetes, hypertension), adjusted cumulative odd ratio (ACOR) and 95% confidence interval (CI) for greater fibrosis severity was 1.4 (0.9, 2.1) (P = 0.17) for postmenopausal women and 1.6 (1.0, 2.5) (P = 0.03) for men, having premenopausal women as a reference. There was borderline interaction between gender and age group divided by age 50, the average age at menopause in the U.S. (P = 0.08): ACOR and 95% CI of having greater fibrosis severity in men compared to women was 1.8 (1.1, 2.9) for patients with age <50 years (P = 0.02) and 1.2 (0.7, 2.1) for patients with age ≥50 years (P = 0.59).
  
  
  CONCLUSIONS
  Men are at a higher risk of having more severe fibrosis compared to women before menopause, while postmenopausal women have a similar severity of liver fibrosis compared to men. These findings may be explained by the protective effects of estrogen against fibrogenesis.
authors.affiliation: Department of Internal Medicine, University of Arkansas for Medical Science, Little Rock, AR.
authors.forename: Ju Dong
authors.initials: JD
authors.lastname: Yang
authors.forename: Manal F
authors.initials: MF
authors.lastname: Abdelmalek
authors.forename: Herbert
authors.initials: H
authors.lastname: Pang
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Guy
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Smith
authors.forename: Anna Mae
authors.initials: AM
authors.lastname: Diehl
authors.forename: Ayako
authors.initials: A
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000367:Age Factors; D001706:Biopsy; D003430:Cross-Sectional Studies; D015914:Estrogen Replacement Therapy; D005234:Fatty Liver / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000503:physiopathology* / Q000517:prevention & control; D016015:Logistic Models; D008297:Male; D008593:Menopause / Q000502:physiology*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D012720:Severity of Illness Index; D012737:Sex Factors