title: Early menopause is associated with lack of response to antiviral therapy in women with chronic hepatitis C.
abstract: OBJECTIVE
  Chronic hepatitis C (CHC) and liver fibrosis progress more rapidly in men and menopausal women than in women of reproductive age. We investigated the associations among menopause, sustained virologic response (SVR), and liver damage in patients with CHC.
  
  
  METHODS
  We performed a prospective study of 1000 consecutive, treatment-naïve patients 18 years of age and older with compensated liver disease from CHC. Liver biopsy samples were analyzed (for fibrosis, inflammation, and steatosis) before patients received standard antiviral therapy. From women (n = 442), we collected data on the presence, type, and timing of menopause; associated hormone and metabolic features; serum levels of interleukin-6; and hepatic tumor necrosis factor (TNF)-α.
  
  
  RESULTS
  Postmenopausal women achieved SVRs less frequently than women of reproductive age (46.0% vs 67.5%; P < .0001) but as frequently as men (51.1%; P = .283). By multivariate regression analysis, independent significant predictors for women to not achieve an SVR were early menopause (odds ratio [OR], 8.055; 95% confidence interval [CI], 1.834-25.350), levels of γ-glutamyl transpeptidase (OR, 2.165; 95% CI, 1.364-3.436), infection with hepatitis C virus genotype 1 or 4 (OR, 3.861; 95% CI, 2.433-6.134), and cholesterol levels (OR, 0.985; 95% CI, 0.971-0.998). Early menopause was the only independent factor that predicted lack of an SVR among women with genotype 1 hepatitis C virus infection (OR, 3.933; 95% CI, 1.274-12.142). Baseline levels of liver inflammation, fibrosis, steatosis, serum interleukin-6 (P = .04), and hepatic TNF-α (P = .007) were significantly higher among postmenopausal women than women of reproductive age.
  
  
  CONCLUSIONS
  Among women with CHC, early menopause was associated with a low likelihood of SVR, probably because of inflammatory factors that change at menopause.
authors.affiliation: Department of Gastroenterology, University of Modena and Reggio Emilia, Modena, Italy. erica.villa@unimore.it
authors.forename: Erica
authors.initials: E
authors.lastname: Villa
authors.forename: Aimilia
authors.initials: A
authors.lastname: Karampatou
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
authors.forename: Monica
authors.initials: M
authors.lastname: Luongo
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrari
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.forename: Luisa
authors.initials: L
authors.lastname: Losi
authors.forename: Gloria
authors.initials: G
authors.lastname: Taliani
authors.forename: Paolo
authors.initials: P
authors.lastname: Trande
authors.forename: Barbara
authors.initials: B
authors.lastname: Lei
authors.forename: Amalia
authors.initials: A
authors.lastname: Graziosi
authors.forename: Veronica
authors.initials: V
authors.lastname: Bernabucci
authors.forename: Rosina
authors.initials: R
authors.lastname: Critelli
authors.forename: Paola
authors.initials: P
authors.lastname: Pazienza
authors.forename: Maria
authors.initials: M
authors.lastname: Rendina
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Francavilla
mesh_terms: D000328:Adult; D000367:Age Factors; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007558:Italy; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000821:virology; D016015:Logistic Models; D008297:Male; D008594:Menopause, Premature / Q000276:immunology; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D013997:Time Factors; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha