Monika Sarkar1, Jennifer L Dodge2, Ruth M Greenblatt3, Mark H Kuniholm4, Jack DeHovitz5, Michael Plankey6, Andrea Kovacs7, Audrey L French8, Eric C Seaberg9, Igho Ofotokun10, Margaret Fischl11, Edgar Overton12, Erin Kelly13, Peter Bacchetti14, Marion G Peters1. 1. Division of GI/Hepatology. 2. Department of Surgery. 3. Department of Pharmacy, University of California, San Francisco (UCSF). 4. Department of Epidemiology & Biostatistics, University at Albany, State University of New York. 5. Division of Infectious Diseases, SUNY Downstate, Brooklyn, New York. 6. Division of Infectious Diseases, Georgetown University, Washington D.C. 7. Division of Infectious Diseases, University of Southern California, Los Angeles. 8. Division of Infectious Diseases, Cook County Hospital, Chicago, Illinois. 9. Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 10. Division of Infectious Diseases, Emory University, Atlanta, Georgia. 11. Division of Infectious Diseases, University of Miami, Florida. 12. Infectious Diseases, University of Alabama, Birmingham. 13. Division of GI/Hepatology, University of Ottawa, Ontario, Canada. 14. Department of Epidemiology & Biostatistics, University of California, San Francisco (UCSF).
Abstract
BACKGROUND: Severity of hepatic fibrosis is greater in postmenopausal than in premenopausal women, perhaps owing to protective effects of estrogens. However, prior studies of estrogen and liver fibrosis lack serial fibrosis measures, adjustment for age, or longitudinal observations in coinfected populations. METHODS: In a longitudinal cohort of women coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), we assessed fibrosis progression across reproductive age, using validated serum fibrosis markers, aminotransferase platelet ratio index (APRI) and fibrosis 4 (FIB-4). Fibrosis rate was evaluated within each woman as she transitioned from pre- to postmenopause, defined by a biomarker of ovarian function. RESULTS: The median follow-up (n = 405) was 9.1 years (interquartile range, 5.0-15.2 years), with a median menopausal age of 49 years (47-52 years). When fully controlled for chronologic aging, the fibrosis progression rate was accelerated during perimenopause, as shown using FIB-4 (0.12 units per year faster than during premenopause; 95% confidence interval [CI], .02-.21; P = .01) and APRI (0.05 units per year faster; -.002 to .09; P = .06). Accelerated fibrosis was also observed during postmenopause compared with premenopause, for FIB-4 (0.14 units per year faster; 95% CI, -.01 to .29; P = .07) and APRI (0.07 units per year faster; -.003 to .15; P = .06). Accelerated fibrosis in perimenopause persisted after adjustment for Hispanic ethnicity, antiretroviral use, and alcohol (0.10 FIB-4 units per year faster than during premenopause; 95% CI, .008-.20; P = .03). CONCLUSIONS: In HIV/HCV-coinfected women, hepatic fibrosis accelerates with reproductive aging. Accelerated fibrosis begins in perimenopause, highlighting a previously unrecognized group of women at increased risk for advanced fibrosis and associated complications. Longitudinal analyses of fibrosis rates across reproductive age should be conducted in non-HCV-related liver diseases, given potential implications in a broader spectrum of women.
BACKGROUND: Severity of hepatic fibrosis is greater in postmenopausal than in premenopausal women, perhaps owing to protective effects of estrogens. However, prior studies of estrogen and liver fibrosis lack serial fibrosis measures, adjustment for age, or longitudinal observations in coinfected populations. METHODS: In a longitudinal cohort of women coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), we assessed fibrosis progression across reproductive age, using validated serum fibrosis markers, aminotransferase platelet ratio index (APRI) and fibrosis 4 (FIB-4). Fibrosis rate was evaluated within each woman as she transitioned from pre- to postmenopause, defined by a biomarker of ovarian function. RESULTS: The median follow-up (n = 405) was 9.1 years (interquartile range, 5.0-15.2 years), with a median menopausal age of 49 years (47-52 years). When fully controlled for chronologic aging, the fibrosis progression rate was accelerated during perimenopause, as shown using FIB-4 (0.12 units per year faster than during premenopause; 95% confidence interval [CI], .02-.21; P = .01) and APRI (0.05 units per year faster; -.002 to .09; P = .06). Accelerated fibrosis was also observed during postmenopause compared with premenopause, for FIB-4 (0.14 units per year faster; 95% CI, -.01 to .29; P = .07) and APRI (0.07 units per year faster; -.003 to .15; P = .06). Accelerated fibrosis in perimenopause persisted after adjustment for Hispanic ethnicity, antiretroviral use, and alcohol (0.10 FIB-4 units per year faster than during premenopause; 95% CI, .008-.20; P = .03). CONCLUSIONS: In HIV/HCV-coinfected women, hepatic fibrosis accelerates with reproductive aging. Accelerated fibrosis begins in perimenopause, highlighting a previously unrecognized group of women at increased risk for advanced fibrosis and associated complications. Longitudinal analyses of fibrosis rates across reproductive age should be conducted in non-HCV-related liver diseases, given potential implications in a broader spectrum of women.
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