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Reproductive Aging and Hepatic Fibrosis Progression in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Women. 2017

Monika Sarkar, and Jennifer L Dodge, and Ruth M Greenblatt, and Mark H Kuniholm, and Jack DeHovitz, and Michael Plankey, and Andrea Kovacs, and Audrey L French, and Eric C Seaberg, and Igho Ofotokun, and Margaret Fischl, and Edgar Overton, and Erin Kelly, and Peter Bacchetti, and Marion G Peters, and
Division of GI/Hepatology.

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.

UI MeSH Term Description Entries
D008103 Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. Cirrhosis, Liver,Fibrosis, Liver,Hepatic Cirrhosis,Liver Fibrosis,Cirrhosis, Hepatic
D008137 Longitudinal Studies Studies in which variables relating to an individual or group of individuals are assessed over a period of time. Bogalusa Heart Study,California Teachers Study,Framingham Heart Study,Jackson Heart Study,Longitudinal Survey,Tuskegee Syphilis Study,Bogalusa Heart Studies,California Teachers Studies,Framingham Heart Studies,Heart Studies, Bogalusa,Heart Studies, Framingham,Heart Studies, Jackson,Heart Study, Bogalusa,Heart Study, Framingham,Heart Study, Jackson,Jackson Heart Studies,Longitudinal Study,Longitudinal Surveys,Studies, Bogalusa Heart,Studies, California Teachers,Studies, Jackson Heart,Studies, Longitudinal,Study, Bogalusa Heart,Study, California Teachers,Study, Longitudinal,Survey, Longitudinal,Surveys, Longitudinal,Syphilis Studies, Tuskegee,Syphilis Study, Tuskegee,Teachers Studies, California,Teachers Study, California,Tuskegee Syphilis Studies
D008593 Menopause The last menstrual period. Permanent cessation of menses (MENSTRUATION) is usually defined after 6 to 12 months of AMENORRHEA in a woman over 45 years of age. In the United States, menopause generally occurs in women between 48 and 55 years of age. Change of Life, Female
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D005260 Female Females
D006526 Hepatitis C INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown. Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted,Parenterally-Transmitted Non-A, Non-B Hepatitis,PT-NANBH,Parenterally Transmitted Non A, Non B Hepatitis
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human

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