Division of GI/Hepatology, University of California San Francisco (UCSF).
Department of Surgery, UCSF.CLD_HCV_Women_Sa
Department of Pharmacy, UCSF.
Department of Epidemiology & Biostatistics, University at Albany, State University of New York, Rensselaer, NY.
Division of Infectious Diseases, SUNY Downstate.
Division of Infectious Diseases, Georgetown University.
Division of Infectious Diseases, University of Southern California.
Division of Infectious Diseases, Cook County Hospital.
Johns Hopkins Bloomberg School of Public Health.
Division of Infectious Diseases, Emory University.
Division of Infectious Diseases, University of Miami.
Infectious Diseases, University of Alabama, Birmingham.
Division of GI/Hepatology, University of Ottawa.
Department of Epidemiology & Biostatistics, UCSF.
Severity of hepatic fibrosis is greater in post- as compared to pre-menopausal women, perhaps due to protective effects of estrogens. However, prior studies of estrogen and liver fibrosis lack serial fibrosis measures, adjustment for age, or longitudinal observations in co-infected populations.
In a longitudinal cohort of HIV/HCV co-infected women we assessed fibrosis progression across reproductive age using validated serum fibrosis markers, APRI and FIB-4. Fibrosis rate was evaluated within each woman as she transitioned from pre- to post-menopausal years, defined by a biomarker of ovarian function.
Median follow-up (n=405) was 9.1 years (IQR 5.0-15.2) with median menopausal age of 49 (IQR 47-52). When fully controlled for chronologic aging, fibrosis progression rate was accelerated during peri-menopausal years using FIB-4 (0.12 units/year faster than pre-menopause, 95% CI 0.02-0.21, p=0.01), and APRI (0.05 units/year faster, 95% CI -0.002-0.09, p=0.06). Accelerated fibrosis was also observed during post- compared to pre-menopausal years for FIB-4 (0.14 units/year faster, 95% CI -0.01-0.29, p=0.07) and APRI (0.07 units/year faster, 95% CI -0.003-0.15, p=0.06). Accelerated fibrosis in peri-menopausal years persisted after adjustment for Hispanic ethnicity, antiretroviral use, and alcohol (0.10 FIB-4 units/year faster than pre-menopause, 95% CI 0.008-0.20, p=0.034).
In HIV/HCV co-infected women, hepatic fibrosis accelerates with reproductive aging. Accelerated fibrosis begins in peri-menopause, 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.