title: Elevated circulating osteoprotegerin and reduced matrix-metalloprotease-9 in post-menopausal women with chronic Hepatitis C virus infection.
abstract: The failure of the immune response to clear the Hepatitis C virus (HCV) results in chronic inflammation that leads to liver cirrhosis. In general, women have a better prognosis than men and this may be associated with increased levels of anti-inflammatory mediators that are positively regulated by female sex hormones. Our aim was to determine if a cohort of Irish women who acquired infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source, had altered levels of circulating cytokine levels compared to women who spontaneously resolved infection, men with HCV infection or age-matched healthy controls. Twenty post-menopausal women and 20 men with chronic HCV infection (genotype 1), 20 post-menopausal women who resolved infection and age and sex-matched controls were recruited for the study. Levels of circulating cytokines were assessed by ELISA. Circulating IL-6, Oncostatin-M, TNF-α, CXCL10, CCL18, VEGF and GM-CSF did not differ between groups. Both men and women with HCV had significantly elevated levels of circulating Osteoprotegerin (OPG). However, male but not female HCV patients had elevated levels of circulating Matrix Metalloprotease-9 (MMP-9). An increased OPG: MMP-9 ratio in the circulation of females compared to males with chronic HCV may help protect against HCV-associated liver disease and explain the slow progress of liver disease in this cohort.
authors.affiliation: National Liver Transplantation Unit, St. Vincent's Hospital, Dublin 4, Ireland.
authors.forename: Kavinderjit S
authors.initials: KS
authors.lastname: Nanda
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Brady
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Murray
authors.forename: Owen
authors.initials: O
authors.lastname: Sullivan
authors.forename: Ursula
authors.initials: U
authors.lastname: Fearon
authors.forename: Malachi J
authors.initials: MJ
authors.lastname: McKenna
authors.forename: John E
authors.initials: JE
authors.lastname: Hegarty
authors.forename: Cliona
authors.initials: C
authors.lastname: O'Farrelly
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Ryan
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000201:enzymology*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D017698:Postmenopause / Q000097:blood*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053244:Osteoprotegerin; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D020780:Matrix Metalloproteinase 9